Molecule Information

General Information of the Molecule (ID: Mol01039)
Name
Penicillin-binding protein 2X (PBP2X) ,Streptococcus pneumoniae
Synonyms
PBP-2X; PBP2X; spr0304
    Click to Show/Hide
Molecule Type
Protein
Gene Name
pbpX
Gene ID
60232761
Sequence
MKWTKRVIRYATKNRKSPAENRRRVGKSLSLLSVFVFAIFLVNFAVIIGTGTRFGTDLAK
EAKKVHQTTRTVPAKRGTIYDRNGVPIAEDATSYNVYAVIDENYKSATGKILYVEKTQFN
KVAEVFHKYLDMEESYVREQLSQPNLKQVSFGAKGNGITYANMMSIKKELEAAEVKGIDF
TTSPNRSYPNGQFASSFIGLAQLHENEDGSKSLLGTSGMESSLNSILAGTDGIITYEKDR
LGNIVPGTEQVSQRTMDGKDVYTTISSPLQSFMETQMDAFQEKVKGKYMTATLVSAKTGE
ILATTQRPTFDADTKEGITEDFVWRDILYQSNYEPGSTMKVMMLAAAIDNNTFPGGEVFN
SSELKIADATIRDWDVNEGLTGGRMMTFSQGFAHSSNVGMTLLEQKMGDATWLDYLNRFK
FGVPTRFGLTDEYAGQLPADNIVNIAQSSFGQGISVTQTQMIRAFTAIANDGVMLEPKFI
SAIYDPNDQTARKSQKEIVGNPVSKDAASLTRTNMVLVGTDPVYGTMYNHSTGKPTVTVP
GQNVALKSGTAQIADEKNGGYLVGLTDYIFSAVSMSPAENPDFILYVTVQQPEHYSGIQL
GEFANPILERASAMKDSLNLQTTAKALEQVSQQSPYPMPSVKDISPGDLAEELRRNLVQP
IVVGTGTKIKNSSAEEGKNLAPNQQVLILSDKAEEVPDMYGWTKETAETLAKWLNIELEF
QGSGSTVQKQDVRANTAIKDIKKITLTLGD
    Click to Show/Hide
3D-structure
PDB ID
5OIZ
Classification
Antibiotic
Method
X-ray diffraction
Resolution
2.70  Å
Function
A transpeptidase that forms peptide cross-links between adjacent glycan strands in cell wall peptidoglycan (PG). Part of the divisome machinery that synthesizes the septal cross wall. Beta-lactams inactivate the PBPs by acylating an essential serine residue in the active site of these proteins.
    Click to Show/Hide
Uniprot ID
PBPX_STRR6
        Click to Show/Hide the Complete Species Lineage
Kingdom: N.A.
Phylum: Firmicutes
Class: Bacilli
Order: Lactobacillales
Family: Streptococcaceae
Genus: Streptococcus
Species: Streptococcus pneumoniae
Type(s) of Resistant Mechanism of This Molecule
  ADTT: Aberration of the Drug's Therapeutic Target
Drug Resistance Data Categorized by Drug
Approved Drug(s)
2 drug(s) in total
Click to Show/Hide the Full List of Drugs
Amoxicillin
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
  Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Disease Class: Streptococcus pneumoniae infection [ICD-11: AA80.2] [1]
Resistant Disease Streptococcus pneumoniae infection [ICD-11: AA80.2]
 Disease Info 
Resistant Drug Amoxicillin
 Drug Info 
Molecule Alteration Missense mutation
p.T338A
Wild Type Structure Method: X-ray diffraction Resolution: 2.66  Å
PDB: 5OJ0
Mutant Type Structure Method: X-ray diffraction Resolution: 2.42  Å
PDB: 1PYY
   Download The Information of Sequence       Download The Structure File   
RMSD: 2.25
TM score: 0.91175
Amino acid change:
T338A
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
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G
G
50
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T
T
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A
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60
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70
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80
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G
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A
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E
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90
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100
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I
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E
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K
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110
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L
L
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120
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K
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A
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F
F
H
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K
Y
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130
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L
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E
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E
140
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N
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L
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V
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150
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G
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160
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Y
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A
N
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M
M
M
M
S
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K
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E
E
170
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L
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E
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D
180
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P
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P
P
190
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N
N
G
G
Q
Q
F
F
A
A
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F
F
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I
G
G
200
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L
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A
A
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L
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H
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E
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E
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G
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210
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S
S
K
K
S
S
L
L
L
L
G
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T
T
S
S
G
G
M
M
220
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E
E
S
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S
S
L
L
N
N
S
S
I
I
L
L
A
A
G
G
230
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T
T
D
D
G
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I
I
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T
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E
E
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D
D
240
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R
R
L
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G
G
N
N
I
I
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G
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E
E
250
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Q
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M
M
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D
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260
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L
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270
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S
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E
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A
280
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F
F
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E
E
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K
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Y
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M
M
290
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T
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A
A
T
T
L
L
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S
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A
A
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T
G
G
300
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E
E
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A
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T
T
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Q
R
R
P
P
T
T
310
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F
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D
D
A
A
D
D
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E
E
G
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T
320
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E
E
D
D
F
F
V
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W
W
R
R
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L
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Y
Y
330
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Q
Q
S
S
N
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Y
Y
E
E
P
P
G
G
S
S
T
A
M
F
340
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K
K
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V
M
M
M
M
L
L
A
A
A
A
A
A
I
I
D
D
350
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N
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N
N
T
T
F
F
P
P
G
G
G
G
E
E
V
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F
F
360
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N
N
S
S
S
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E
L
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I
I
A
A
D
D
A
A
370
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T
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I
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R
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D
W
W
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E
G
G
380
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L
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G
G
G
G
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R
M
M
M
M
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F
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S
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390
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Q
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G
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F
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A
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H
H
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V
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G
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400
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M
M
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L
L
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E
E
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G
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D
D
410
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A
A
T
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W
W
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D
Y
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L
L
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R
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F
420
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K
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F
F
G
G
V
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P
T
T
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L
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430
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T
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A
A
G
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L
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A
A
440
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D
D
N
N
I
I
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I
I
A
A
Q
Q
S
S
S
S
450
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F
F
G
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G
G
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T
460
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M
M
I
I
R
R
A
A
F
F
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T
A
A
I
I
A
A
470
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N
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D
D
G
G
V
V
M
M
L
L
E
E
P
P
K
K
F
F
480
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I
I
S
S
A
A
I
I
Y
Y
D
D
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P
N
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D
D
Q
Q
490
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T
T
A
A
R
R
K
K
S
S
Q
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K
K
E
E
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I
V
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500
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G
G
N
N
P
P
V
V
S
S
K
K
D
D
A
A
A
A
S
S
510
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L
L
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T
R
R
T
T
N
N
M
M
V
V
L
L
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G
G
520
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T
T
D
D
P
P
V
V
Y
Y
G
G
T
T
M
M
Y
Y
N
N
530
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H
H
S
S
T
T
G
G
K
K
P
P
T
T
V
V
T
T
V
V
540
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P
P
G
G
Q
Q
N
N
V
V
A
A
L
L
K
K
S
S
G
G
550
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T
T
A
A
Q
Q
I
I
A
A
D
D
E
E
K
K
N
N
G
G
560
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G
G
Y
Y
L
L
V
V
G
G
L
L
T
T
D
D
Y
Y
I
I
570
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F
F
S
S
A
A
V
V
S
S
M
M
S
S
P
P
A
A
E
E
580
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N
N
P
P
D
D
F
F
I
I
L
L
Y
Y
V
V
T
T
V
V
590
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Q
Q
Q
Q
P
P
E
E
H
H
Y
Y
S
S
G
G
I
I
Q
Q
600
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L
L
G
G
E
E
F
F
A
A
N
N
P
P
I
I
L
L
E
E
610
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R
R
A
A
S
S
A
A
M
M
K
K
D
D
S
S
L
L
N
N
620
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L
L
Q
Q
T
T
T
T
A
A
K
K
A
A
L
L
E
E
Q
Q
630
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V
V
S
S
Q
Q
Q
Q
S
S
P
P
Y
Y
P
P
M
M
P
P
640
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S
S
V
V
K
K
D
D
I
I
S
S
P
P
G
G
D
D
L
L
650
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A
A
E
E
E
E
L
L
R
R
R
R
N
N
L
L
V
V
Q
Q
660
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P
P
I
I
V
V
V
V
G
G
T
T
G
G
T
T
K
K
I
I
670
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K
K
N
N
S
S
S
S
A
A
E
E
E
E
G
G
K
K
N
N
680
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L
L
A
A
P
P
N
N
Q
Q
Q
Q
V
V
L
L
I
I
L
L
690
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S
S
D
D
K
K
A
A
E
E
E
E
V
V
P
P
D
D
M
M
700
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Y
Y
G
G
W
W
T
T
K
K
E
E
T
T
A
A
E
E
T
T
710
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L
L
A
A
K
K
W
W
L
L
N
N
I
I
E
E
L
L
E
E
720
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F
F
Q
Q
G
G
S
S
G
G
S
S
T
T
V
V
Q
Q
K
K
730
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Q
Q
D
D
V
V
R
R
A
A
N
N
T
T
A
A
I
I
K
K
740
|
D
D
I
I
K
K
K
K
I
I
T
T
L
L
T
T
L
L
G
G
750
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D
D
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
In Vitro Model Streptococcus pneumoniae isolates 1313
Experiment for
Molecule Alteration		 PCR amplification and sequence alignments assay
Experiment for
Drug Resistance		 Correspondence discriminant assay
Mechanism Description The efficacy of Beta-lactam antibiotics in Streptococcus pneumoniae has been compromised because of the development of altered penicillin-binding proteins (PBPs).
Disease Class: Streptococcus pneumoniae infection [ICD-11: AA80.2] [1]
Resistant Disease Streptococcus pneumoniae infection [ICD-11: AA80.2]
 Disease Info 
Resistant Drug Amoxicillin
 Drug Info 
Molecule Alteration Missense mutation
p.E320K
Experimental Note Identified from the Human Clinical Data
In Vitro Model Streptococcus pneumoniae isolates 1313
Experiment for
Molecule Alteration		 PCR amplification and sequence alignments assay
Experiment for
Drug Resistance		 Correspondence discriminant assay
Mechanism Description The efficacy of Beta-lactam antibiotics in Streptococcus pneumoniae has been compromised because of the development of altered penicillin-binding proteins (PBPs).
Disease Class: Streptococcus pneumoniae infection [ICD-11: AA80.2] [1]
Resistant Disease Streptococcus pneumoniae infection [ICD-11: AA80.2]
 Disease Info 
Resistant Drug Amoxicillin
 Drug Info 
Molecule Alteration Missense mutation
p.Q552E
Experimental Note Identified from the Human Clinical Data
In Vitro Model Streptococcus pneumoniae isolates 1313
Experiment for
Molecule Alteration		 PCR amplification and sequence alignments assay
Experiment for
Drug Resistance		 Correspondence discriminant assay
Mechanism Description The efficacy of Beta-lactam antibiotics in Streptococcus pneumoniae has been compromised because of the development of altered penicillin-binding proteins (PBPs).
Disease Class: Streptococcus pneumoniae infection [ICD-11: AA80.2] [1]
Resistant Disease Streptococcus pneumoniae infection [ICD-11: AA80.2]
 Disease Info 
Resistant Drug Amoxicillin
 Drug Info 
Molecule Alteration Missense mutation
p.D311N
Experimental Note Identified from the Human Clinical Data
In Vitro Model Streptococcus pneumoniae isolates 1313
Experiment for
Molecule Alteration		 PCR amplification and sequence alignments assay
Experiment for
Drug Resistance		 Correspondence discriminant assay
Mechanism Description The efficacy of Beta-lactam antibiotics in Streptococcus pneumoniae has been compromised because of the development of altered penicillin-binding proteins (PBPs).
Disease Class: Streptococcus pneumoniae infection [ICD-11: AA80.2] [1]
Resistant Disease Streptococcus pneumoniae infection [ICD-11: AA80.2]
 Disease Info 
Resistant Drug Amoxicillin
 Drug Info 
Molecule Alteration Missense mutation
p.M343T
Experimental Note Identified from the Human Clinical Data
In Vitro Model Streptococcus pneumoniae isolates 1313
Experiment for
Molecule Alteration		 PCR amplification and sequence alignments assay
Experiment for
Drug Resistance		 Correspondence discriminant assay
Mechanism Description The efficacy of Beta-lactam antibiotics in Streptococcus pneumoniae has been compromised because of the development of altered penicillin-binding proteins (PBPs).
Disease Class: Streptococcus pneumoniae infection [ICD-11: AA80.2] [1]
Resistant Disease Streptococcus pneumoniae infection [ICD-11: AA80.2]
 Disease Info 
Resistant Drug Amoxicillin
 Drug Info 
Molecule Alteration Missense mutation
p.A491V
Experimental Note Identified from the Human Clinical Data
In Vitro Model Streptococcus pneumoniae isolates 1313
Experiment for
Molecule Alteration		 PCR amplification and sequence alignments assay
Experiment for
Drug Resistance		 Correspondence discriminant assay
Mechanism Description The efficacy of Beta-lactam antibiotics in Streptococcus pneumoniae has been compromised because of the development of altered penicillin-binding proteins (PBPs).
Disease Class: Streptococcus pneumoniae infection [ICD-11: AA80.2] [1]
Resistant Disease Streptococcus pneumoniae infection [ICD-11: AA80.2]
 Disease Info 
Resistant Drug Amoxicillin
 Drug Info 
Molecule Alteration Missense mutation
p.D506E
Experimental Note Identified from the Human Clinical Data
In Vitro Model Streptococcus pneumoniae isolates 1313
Experiment for
Molecule Alteration		 PCR amplification and sequence alignments assay
Experiment for
Drug Resistance		 Correspondence discriminant assay
Mechanism Description The efficacy of Beta-lactam antibiotics in Streptococcus pneumoniae has been compromised because of the development of altered penicillin-binding proteins (PBPs).
Disease Class: Streptococcus pneumoniae infection [ICD-11: AA80.2] [1]
Resistant Disease Streptococcus pneumoniae infection [ICD-11: AA80.2]
 Disease Info 
Resistant Drug Amoxicillin
 Drug Info 
Molecule Alteration Missense mutation
p.T536I
Experimental Note Identified from the Human Clinical Data
In Vitro Model Streptococcus pneumoniae isolates 1313
Experiment for
Molecule Alteration		 PCR amplification and sequence alignments assay
Experiment for
Drug Resistance		 Correspondence discriminant assay
Mechanism Description The efficacy of Beta-lactam antibiotics in Streptococcus pneumoniae has been compromised because of the development of altered penicillin-binding proteins (PBPs).
Disease Class: Streptococcus pneumoniae infection [ICD-11: AA80.2] [1]
Resistant Disease Streptococcus pneumoniae infection [ICD-11: AA80.2]
 Disease Info 
Resistant Drug Amoxicillin
 Drug Info 
Molecule Alteration Missense mutation
p.V641I
Experimental Note Identified from the Human Clinical Data
In Vitro Model Streptococcus pneumoniae isolates 1313
Experiment for
Molecule Alteration		 PCR amplification and sequence alignments assay
Experiment for
Drug Resistance		 Correspondence discriminant assay
Mechanism Description The efficacy of Beta-lactam antibiotics in Streptococcus pneumoniae has been compromised because of the development of altered penicillin-binding proteins (PBPs).
Disease Class: Streptococcus pneumoniae infection [ICD-11: AA80.2] [1]
Resistant Disease Streptococcus pneumoniae infection [ICD-11: AA80.2]
 Disease Info 
Resistant Drug Amoxicillin
 Drug Info 
Molecule Alteration Missense mutation
p.L657I
Experimental Note Identified from the Human Clinical Data
In Vitro Model Streptococcus pneumoniae isolates 1313
Experiment for
Molecule Alteration		 PCR amplification and sequence alignments assay
Experiment for
Drug Resistance		 Correspondence discriminant assay
Mechanism Description The efficacy of Beta-lactam antibiotics in Streptococcus pneumoniae has been compromised because of the development of altered penicillin-binding proteins (PBPs).
Disease Class: Streptococcus pneumoniae infection [ICD-11: AA80.2] [1]
Resistant Disease Streptococcus pneumoniae infection [ICD-11: AA80.2]
 Disease Info 
Resistant Drug Amoxicillin
 Drug Info 
Molecule Alteration Missense mutation
p.A693V
Experimental Note Identified from the Human Clinical Data
In Vitro Model Streptococcus pneumoniae isolates 1313
Experiment for
Molecule Alteration		 PCR amplification and sequence alignments assay
Experiment for
Drug Resistance		 Correspondence discriminant assay
Mechanism Description The efficacy of Beta-lactam antibiotics in Streptococcus pneumoniae has been compromised because of the development of altered penicillin-binding proteins (PBPs).
Disease Class: Streptococcus pneumoniae infection [ICD-11: AA80.2] [1]
Resistant Disease Streptococcus pneumoniae infection [ICD-11: AA80.2]
 Disease Info 
Resistant Drug Amoxicillin
 Drug Info 
Molecule Alteration Missense mutation
p.T703K
Experimental Note Identified from the Human Clinical Data
In Vitro Model Streptococcus pneumoniae isolates 1313
Experiment for
Molecule Alteration		 PCR amplification and sequence alignments assay
Experiment for
Drug Resistance		 Correspondence discriminant assay
Mechanism Description The efficacy of Beta-lactam antibiotics in Streptococcus pneumoniae has been compromised because of the development of altered penicillin-binding proteins (PBPs).
Disease Class: Streptococcus pneumoniae infection [ICD-11: AA80.2] [1]
Resistant Disease Streptococcus pneumoniae infection [ICD-11: AA80.2]
 Disease Info 
Resistant Drug Amoxicillin
 Drug Info 
Molecule Alteration Missense mutation
p.L710F
Experimental Note Identified from the Human Clinical Data
In Vitro Model Streptococcus pneumoniae isolates 1313
Experiment for
Molecule Alteration		 PCR amplification and sequence alignments assay
Experiment for
Drug Resistance		 Correspondence discriminant assay
Mechanism Description The efficacy of Beta-lactam antibiotics in Streptococcus pneumoniae has been compromised because of the development of altered penicillin-binding proteins (PBPs).
Disease Class: Streptococcus pneumoniae infection [ICD-11: AA80.2] [1]
Resistant Disease Streptococcus pneumoniae infection [ICD-11: AA80.2]
 Disease Info 
Resistant Drug Amoxicillin
 Drug Info 
Molecule Alteration Missense mutation
p.D740N
Experimental Note Identified from the Human Clinical Data
In Vitro Model Streptococcus pneumoniae isolates 1313
Experiment for
Molecule Alteration		 PCR amplification and sequence alignments assay
Experiment for
Drug Resistance		 Correspondence discriminant assay
Mechanism Description The efficacy of Beta-lactam antibiotics in Streptococcus pneumoniae has been compromised because of the development of altered penicillin-binding proteins (PBPs).
Disease Class: Streptococcus pneumoniae infection [ICD-11: AA80.2] [1]
Resistant Disease Streptococcus pneumoniae infection [ICD-11: AA80.2]
 Disease Info 
Resistant Drug Amoxicillin
 Drug Info 
Molecule Alteration Missense mutation
p.T745K
Experimental Note Identified from the Human Clinical Data
In Vitro Model Streptococcus pneumoniae isolates 1313
Experiment for
Molecule Alteration		 PCR amplification and sequence alignments assay
Experiment for
Drug Resistance		 Correspondence discriminant assay
Mechanism Description The efficacy of Beta-lactam antibiotics in Streptococcus pneumoniae has been compromised because of the development of altered penicillin-binding proteins (PBPs).
Disease Class: Streptococcus pneumoniae infection [ICD-11: AA80.2] [1]
Resistant Disease Streptococcus pneumoniae infection [ICD-11: AA80.2]
 Disease Info 
Resistant Drug Amoxicillin
 Drug Info 
Molecule Alteration Missense mutation
p.Q629K
Experimental Note Identified from the Human Clinical Data
In Vitro Model Streptococcus pneumoniae isolates 1313
Experiment for
Molecule Alteration		 PCR amplification and sequence alignments assay
Experiment for
Drug Resistance		 Correspondence discriminant assay
Mechanism Description The efficacy of Beta-lactam antibiotics in Streptococcus pneumoniae has been compromised because of the development of altered penicillin-binding proteins (PBPs).
Disease Class: Streptococcus pneumoniae infection [ICD-11: AA80.2] [1]
Resistant Disease Streptococcus pneumoniae infection [ICD-11: AA80.2]
 Disease Info 
Resistant Drug Amoxicillin
 Drug Info 
Molecule Alteration Missense mutation
p.Q632T
Experimental Note Identified from the Human Clinical Data
In Vitro Model Streptococcus pneumoniae isolates 1313
Experiment for
Molecule Alteration		 PCR amplification and sequence alignments assay
Experiment for
Drug Resistance		 Correspondence discriminant assay
Mechanism Description The efficacy of Beta-lactam antibiotics in Streptococcus pneumoniae has been compromised because of the development of altered penicillin-binding proteins (PBPs).
Ceftobiprole
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
  Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Disease Class: Community-acquired pneumonia [ICD-11: CA40.2] [2], [3], [4]
Resistant Disease Community-acquired pneumonia [ICD-11: CA40.2]
 Disease Info 
Resistant Drug Ceftobiprole
 Drug Info 
Molecule Alteration Missense mutation
p.M339F
Wild Type Structure Method: X-ray diffraction Resolution: 2.66  Å
PDB: 5OJ0
Mutant Type Structure Method: X-ray diffraction Resolution: 2.42  Å
PDB: 1PYY
   Download The Information of Sequence       Download The Structure File   
RMSD: 2.25
TM score: 0.91175
Amino acid change:
M339F
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
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G
G
50
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T
T
G
G
T
T
R
R
F
F
G
G
T
T
D
D
L
L
A
A
60
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K
K
E
E
A
A
K
K
K
K
V
V
H
H
Q
Q
T
T
T
T
70
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R
R
T
T
V
V
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P
A
A
K
K
R
R
G
G
T
T
I
I
80
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Y
Y
D
D
R
R
N
N
G
G
V
V
P
P
I
I
A
A
E
E
90
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D
D
A
A
T
T
S
S
Y
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N
N
V
V
Y
Y
A
A
V
V
100
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I
I
D
D
E
E
N
N
Y
Y
K
K
S
S
A
A
T
T
G
G
110
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K
K
I
I
L
L
Y
Y
V
V
E
E
K
K
T
T
Q
Q
F
F
120
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N
N
K
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V
V
A
A
E
E
V
V
F
F
H
H
K
K
Y
Y
130
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L
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M
E
E
E
E
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Y
Y
V
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E
E
140
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L
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S
S
Q
Q
P
P
N
N
L
L
K
K
Q
Q
V
V
150
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S
S
F
F
G
G
A
A
K
K
G
G
N
N
G
G
I
I
T
T
160
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Y
Y
A
A
N
N
M
M
M
M
S
S
I
I
K
K
K
K
E
E
170
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L
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E
E
A
A
A
A
E
E
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K
K
G
G
I
I
D
D
180
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F
F
T
T
T
T
S
S
P
P
N
N
R
R
S
S
Y
Y
P
P
190
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N
N
G
G
Q
Q
F
F
A
A
S
S
S
S
F
F
I
I
G
G
200
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L
L
A
A
Q
Q
L
L
H
H
E
E
N
N
E
E
D
D
G
G
210
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S
S
K
K
S
S
L
L
L
L
G
G
T
T
S
S
G
G
M
M
220
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E
E
S
S
S
S
L
L
N
N
S
S
I
I
L
L
A
A
G
G
230
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T
T
D
D
G
G
I
I
I
I
T
T
Y
Y
E
E
K
K
D
D
240
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R
R
L
L
G
G
N
N
I
I
V
V
P
P
G
G
T
T
E
E
250
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Q
Q
V
V
S
S
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Q
R
R
T
T
M
M
D
D
G
G
K
K
260
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D
D
V
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Y
Y
T
T
T
T
I
I
S
S
S
S
P
P
L
L
270
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Q
Q
S
S
F
F
M
M
E
E
T
T
Q
Q
M
M
D
D
A
A
280
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F
F
Q
Q
E
E
K
K
V
V
K
K
G
G
K
K
Y
Y
M
M
290
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T
T
A
A
T
T
L
L
V
V
S
S
A
A
K
K
T
T
G
G
300
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E
E
I
I
L
L
A
A
T
T
T
T
Q
Q
R
R
P
P
T
T
310
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F
F
D
D
A
A
D
D
T
T
K
K
E
E
G
G
I
I
T
T
320
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E
E
D
D
F
F
V
V
W
W
R
R
D
D
I
I
L
L
Y
Y
330
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Q
Q
S
S
N
N
Y
Y
E
E
P
P
G
G
S
S
T
A
M
F
340
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K
K
V
V
M
M
M
M
L
L
A
A
A
A
A
A
I
I
D
D
350
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N
N
N
N
T
T
F
F
P
P
G
G
G
G
E
E
V
V
F
F
360
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N
N
S
S
S
S
E
E
L
L
K
K
I
I
A
A
D
D
A
A
370
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T
T
I
I
R
R
D
D
W
W
D
D
V
V
N
N
E
E
G
G
380
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L
L
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T
G
G
G
G
R
R
M
M
M
M
T
T
F
F
S
S
390
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Q
Q
G
G
F
F
A
A
H
H
S
S
S
S
N
N
V
V
G
G
400
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M
M
T
T
L
L
L
L
E
E
Q
Q
K
K
M
M
G
G
D
D
410
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A
A
T
T
W
W
L
L
D
D
Y
Y
L
L
N
N
R
R
F
F
420
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K
K
F
F
G
G
V
V
P
P
T
T
R
R
F
F
G
G
L
L
430
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T
T
D
D
E
E
Y
Y
A
A
G
G
Q
Q
L
L
P
P
A
A
440
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D
D
N
N
I
I
V
V
N
N
I
I
A
A
Q
Q
S
S
S
S
450
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F
F
G
G
Q
Q
G
G
I
I
S
S
V
V
T
T
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Q
T
T
460
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Q
Q
M
M
I
I
R
R
A
A
F
F
T
T
A
A
I
I
A
A
470
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N
N
D
D
G
G
V
V
M
M
L
L
E
E
P
P
K
K
F
F
480
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I
I
S
S
A
A
I
I
Y
Y
D
D
P
P
N
N
D
D
Q
Q
490
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T
T
A
A
R
R
K
K
S
S
Q
Q
K
K
E
E
I
I
V
V
500
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G
G
N
N
P
P
V
V
S
S
K
K
D
D
A
A
A
A
S
S
510
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L
L
T
T
R
R
T
T
N
N
M
M
V
V
L
L
V
V
G
G
520
|
T
T
D
D
P
P
V
V
Y
Y
G
G
T
T
M
M
Y
Y
N
N
530
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H
H
S
S
T
T
G
G
K
K
P
P
T
T
V
V
T
T
V
V
540
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P
P
G
G
Q
Q
N
N
V
V
A
A
L
L
K
K
S
S
G
G
550
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T
T
A
A
Q
Q
I
I
A
A
D
D
E
E
K
K
N
N
G
G
560
|
G
G
Y
Y
L
L
V
V
G
G
L
L
T
T
D
D
Y
Y
I
I
570
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F
F
S
S
A
A
V
V
S
S
M
M
S
S
P
P
A
A
E
E
580
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N
N
P
P
D
D
F
F
I
I
L
L
Y
Y
V
V
T
T
V
V
590
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Q
Q
Q
Q
P
P
E
E
H
H
Y
Y
S
S
G
G
I
I
Q
Q
600
|
L
L
G
G
E
E
F
F
A
A
N
N
P
P
I
I
L
L
E
E
610
|
R
R
A
A
S
S
A
A
M
M
K
K
D
D
S
S
L
L
N
N
620
|
L
L
Q
Q
T
T
T
T
A
A
K
K
A
A
L
L
E
E
Q
Q
630
|
V
V
S
S
Q
Q
Q
Q
S
S
P
P
Y
Y
P
P
M
M
P
P
640
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S
S
V
V
K
K
D
D
I
I
S
S
P
P
G
G
D
D
L
L
650
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A
A
E
E
E
E
L
L
R
R
R
R
N
N
L
L
V
V
Q
Q
660
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P
P
I
I
V
V
V
V
G
G
T
T
G
G
T
T
K
K
I
I
670
|
K
K
N
N
S
S
S
S
A
A
E
E
E
E
G
G
K
K
N
N
680
|
L
L
A
A
P
P
N
N
Q
Q
Q
Q
V
V
L
L
I
I
L
L
690
|
S
S
D
D
K
K
A
A
E
E
E
E
V
V
P
P
D
D
M
M
700
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Y
Y
G
G
W
W
T
T
K
K
E
E
T
T
A
A
E
E
T
T
710
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L
L
A
A
K
K
W
W
L
L
N
N
I
I
E
E
L
L
E
E
720
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F
F
Q
Q
G
G
S
S
G
G
S
S
T
T
V
V
Q
Q
K
K
730
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Q
Q
D
D
V
V
R
R
A
A
N
N
T
T
A
A
I
I
K
K
740
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D
D
I
I
K
K
K
K
I
I
T
T
L
L
T
T
L
L
G
G
750
|
D
D
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
In Vitro Model Streptococcus pneumoniae isolates 1313
Experiment for
Molecule Alteration		 Genome sequence assay
Experiment for
Drug Resistance		 MIC assay
Mechanism Description Beta-Lactam resistance in S. pneumoniae is caused by mutations in the penicillin-binding domains of one or more of its six penicillin-binding proteins (PBPs) resulting from point mutations or mosaic genes. Altered PBP 1a, PBP 2x, and PBP 2b are the most important PBPs for Beta-lactam resistance among clinical isolates.
Disease Class: Community-acquired pneumonia [ICD-11: CA40.2] [2], [3], [4]
Resistant Disease Community-acquired pneumonia [ICD-11: CA40.2]
 Disease Info 
Resistant Drug Ceftobiprole
 Drug Info 
Molecule Alteration Missense mutation
p.I371T
Experimental Note Identified from the Human Clinical Data
In Vitro Model Streptococcus pneumoniae isolates 1313
Experiment for
Molecule Alteration		 Genome sequence assay
Experiment for
Drug Resistance		 MIC assay
Mechanism Description Beta-Lactam resistance in S. pneumoniae is caused by mutations in the penicillin-binding domains of one or more of its six penicillin-binding proteins (PBPs) resulting from point mutations or mosaic genes. Altered PBP 1a, PBP 2x, and PBP 2b are the most important PBPs for Beta-lactam resistance among clinical isolates.
Disease Class: Community-acquired pneumonia [ICD-11: CA40.2] [2], [3], [4]
Resistant Disease Community-acquired pneumonia [ICD-11: CA40.2]
 Disease Info 
Resistant Drug Ceftobiprole
 Drug Info 
Molecule Alteration Missense mutation
p.R384G
Experimental Note Identified from the Human Clinical Data
In Vitro Model Streptococcus pneumoniae isolates 1313
Experiment for
Molecule Alteration		 Genome sequence assay
Experiment for
Drug Resistance		 MIC assay
Mechanism Description Beta-Lactam resistance in S. pneumoniae is caused by mutations in the penicillin-binding domains of one or more of its six penicillin-binding proteins (PBPs) resulting from point mutations or mosaic genes. Altered PBP 1a, PBP 2x, and PBP 2b are the most important PBPs for Beta-lactam resistance among clinical isolates.
Disease Class: Community-acquired pneumonia [ICD-11: CA40.2] [2], [3], [4]
Resistant Disease Community-acquired pneumonia [ICD-11: CA40.2]
 Disease Info 
Resistant Drug Ceftobiprole
 Drug Info 
Molecule Alteration Missense mutation
p.M400T
Experimental Note Identified from the Human Clinical Data
In Vitro Model Streptococcus pneumoniae isolates 1313
Experiment for
Molecule Alteration		 Genome sequence assay
Experiment for
Drug Resistance		 MIC assay
Mechanism Description Beta-Lactam resistance in S. pneumoniae is caused by mutations in the penicillin-binding domains of one or more of its six penicillin-binding proteins (PBPs) resulting from point mutations or mosaic genes. Altered PBP 1a, PBP 2x, and PBP 2b are the most important PBPs for Beta-lactam resistance among clinical isolates.
Disease Class: Community-acquired pneumonia [ICD-11: CA40.2] [2], [3], [4]
Resistant Disease Community-acquired pneumonia [ICD-11: CA40.2]
 Disease Info 
Resistant Drug Ceftobiprole
 Drug Info 
Molecule Alteration Missense mutation
STMK motif p.M>F
Experimental Note Identified from the Human Clinical Data
In Vitro Model Streptococcus pneumoniae isolates 1313
Experiment for
Molecule Alteration		 Genome sequence assay
Experiment for
Drug Resistance		 MIC assay
Mechanism Description Beta-Lactam resistance in S. pneumoniae is caused by mutations in the penicillin-binding domains of one or more of its six penicillin-binding proteins (PBPs) resulting from point mutations or mosaic genes. Altered PBP 1a, PBP 2x, and PBP 2b are the most important PBPs for Beta-lactam resistance among clinical isolates.
References
Ref 1 Positive selection in penicillin-binding proteins 1a, 2b, and 2x from Streptococcus pneumoniae and its correlation with amoxicillin resistance development. Infect Genet Evol. 2008 May;8(3):331-9. doi: 10.1016/j.meegid.2008.02.001. Epub 2008 Feb 14.
Ref 2 Amino acid substitutions in mosaic penicillin-binding protein 2 associated with reduced susceptibility to cefixime in clinical isolates of Neisseria gonorrhoeae. Antimicrob Agents Chemother. 2006 Nov;50(11):3638-45. doi: 10.1128/AAC.00626-06. Epub 2006 Aug 28.
Ref 3 Resistance to Beta-Lactams in Neisseria ssp Due to Chromosomally Encoded Penicillin-Binding Proteins. Antibiotics (Basel). 2016 Sep 28;5(4):35. doi: 10.3390/antibiotics5040035.
Ref 4 Crystal structures of penicillin-binding protein 2 from penicillin-susceptible and -resistant strains of Neisseria gonorrhoeae reveal an unexpectedly subtle mechanism for antibiotic resistance. J Biol Chem. 2009 Jan 9;284(2):1202-12. doi: 10.1074/jbc.M805761200. Epub 2008 Nov 4.

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