Drug Information

Drug (ID: DG00574) and It's Reported Resistant Information
Name
Levedopa
Synonyms
Levodopa; L-dopa; 59-92-7; 3,4-dihydroxy-L-phenylalanine; 3-Hydroxy-L-tyrosine; Dopar; Bendopa; Larodopa; Levopa; Brocadopa; Cidandopa; Insulamina; Maipedopa; Dopaidan; Dopalina; Dopasol; Eldopal; Eldopar; Pardopa; Prodopa; Syndopa; 3-(3,4-Dihydroxyphenyl)-L-alanine; 3,4-Dihydroxyphenylalanine; (-)-Dopa; Dihydroxy-L-phenylalanine; Helfo-Dopa; Dopaflex; Deadopa; Dopal-fher; Doparkine; Dopaston; Dopastral; Eldopatec; Eurodopa; Doparl; Doprin; Veldopa; (2S)-2-amino-3-(3,4-dihydroxyphenyl)propanoic acid; L-3,4-Dihydroxyphenylalanine; Levedopa; Levodopum; L-o-Hydroxytyrosine; Dopa; Ledopa; (-)-3-(3,4-Dihydroxyphenyl)-L-alanine; L-Tyrosine, 3-hydroxy-; 3,4-Dihydroxyphenyl-L-alanine; Dopaston SE; beta-(3,4-Dihydroxyphenyl)-L-alanine; L-(o-Dihydroxyphenyl)alanine; L-(-)-Dopa; L-3-Hydroxytyrosine; L-beta-(3,4-Dihydroxyphenyl)alanine; Weldopa; Parda; L-Dihydroxyphenylalanine; L-3-(3,4-Dihydroxyphenyl)alanine; C9H11NO4; Ro 4-6316; beta-(3,4-Dihydroxyphenyl)alanine; (S)-2-amino-3-(3,4-dihydroxyphenyl)propanoic acid; alanine, 3-(3,4-dihydroxyphenyl)-, L-; component of Sinemet; Dopar (TN); CHEBI:15765; CVT-301; beta-(3,4-Dihydroxyphenyl)-alpha-L-alanine; L-beta-(3,4-Dihydroxyphenyl)-alpha-alanine; UNII-46627O600J; Alanine, 3-(3,4-dihydroxyphenyl)-, (-)-; L(-)-Dopa; (-)-(3,4-Dihydroxyphenyl)alanine; dihydroxyphenylalanine; MFCD00002598; L-3,4-Dihydrophenylalanine; L-.beta.-(3,4-Dihydroxyphenyl)alanine; CHEMBL1009; .beta.-(3,4-Dihydroxyphenyl)-L-alanine; L-(3,4-Dihydroxyphenyl)alanine; L-Tyrosine, 3-hydroxy-, homopolymer; NSC118381; .beta.-(3,4-Dihydroxyphenyl)alanine; NSC-118381; CAS-59-92-7; NCGC00016270-04; Biodopa; Cerepap; Laradopa; Sobiodopa; L-(3,4-Dihydroxyphenyl)-.alpha.-alanine; 46627O600J; Helfo DOPA; beta-(3,4-Dihydroxyphenyl)-alpha-alanine; Atamet; Levodopum [INN-Latin]; BDBM50130192; L-O-Dihydroxyphenylalanine; L Dopa; 65170-01-6; CCRIS 3766; HSDB 3348; WLN: QVYZ1R CQ DQ; 3,4-Dihydroxyphenylalanine (VAN); SR-01000075384; EINECS 200-445-2; NSC 118381; Dopastone; Dopicar; Inbrija; Prolopa; (2S)-2-amino-3-(3,4-dihydroxyphenyl)propanoate; Prestwick_185; Levodopa (Sinemet); L-DOPA; Levodopa; Madopa (Salt/Mix); Levodopa [USAN:USP:INN:BAN:JAN]; Spectrum_000454; 4-dihydroxyphenylalanine; Carbidopa EP Impurity A; Prestwick0_000017; Prestwick1_000017; Prestwick2_000017; Prestwick3_000017; Spectrum2_000496; Spectrum4_000539; Spectrum5_001899; Lopac-D-9628; Levodopa (JP15/USP); DSSTox_CID_3209; bmse000322; Epitope ID:150927; 3, 4-Dihydroxyphenylalanine; Alanine,4-dihydroxyphenyl)-; DSSTox_RID_76926; DSSTox_GSID_23209; Lopac0_000454; SCHEMBL22655; BSPBio_000053; BSPBio_002354; KBioGR_001177; KBioSS_000934; L-4-5-Dihydroxyphenylalanine; MLS000028514; BIDD:GT0158; DivK1c_000452; SPECTRUM2300205; Levodopa (JP17/USP/INN); SPBio_000391; SPBio_001974; BPBio1_000059; GTPL3639; b-(3,4-Dihydroxyphenyl)alanine; DTXSID9023209; WLN: QVYZ1R CQ DQ -L; 3, 4-Dihydroxy-L-phenylalanine; BDBM60928; HMS501G14; KBio1_000452; KBio2_000934; KBio2_003502; KBio2_006070; Alanine,4-dihydroxyphenyl)-, L-; L-(3, 4-Dihydroxyphenyl)alanine; NINDS_000452; 3-Ethoxy-4-fluorophenylboronicacid; HMS1568C15; HMS1922J14; HMS2090O08; HMS2093N04; HMS2095C15; HMS2230B04; HMS3261K10; HMS3712C15; Pharmakon1600-02300205; ZINC895199; H-Phe{3,4-(OH)2}-OH; HY-N0304; Levodopa;3,4-Dihydroxyphenylalanine; b-(3,4-Dihydroxyphenyl)-L-alanine; Inbrija (levodopa inhalation powder); Tox21_110338; Tox21_500454; CCG-39571; L-3-(3,4-dihydroxy-phenyl)alanine; L-3-(3,4-dihydroxyphenyl)-Alanine; NSC759573; PDSP1_001541; PDSP2_001525; s1726; Alanine, 3-(3,4-dihydroxyphenyl)-; Alanine,4-dihydroxyphenyl)-, (-)-; AKOS010396267; b-(3,4-Dihydroxyphenyl)-a-L-alanine; L-b-(3,4-Dihydroxyphenyl)-a-alanine; .beta.-(3, 4-Dihydroxyphenyl)alanine; AC-8432; AM82124; CS-1945; DB01235; LP00454; MCULE-4743781842; NSC-759573; SDCCGMLS-0066924.P001; SDCCGSBI-0050439.P004; IDI1_000452; NCGC00015384-01; NCGC00016270-01; NCGC00016270-06; NCGC00016270-07; NCGC00016270-09; NCGC00016270-10; NCGC00016270-22; NCGC00093869-04; NCGC00261139-01; AS-13287; BP-12850; H813; SMR000058312; SBI-0050439.P003; L-(3, 4-Dihydroxyphenyl)-.alpha.-alanine; D0600; D9628; EU-0100454; N1648; 59L927; Alanine, 3-(3, 4-dihydroxyphenyl)-, (-)-; C00355; D 9628; D00059; D70595; J10404; V-1512; 3,4-Dihydroxy-L-phenylalanine, >=98% (TLC); AB00052418-06; AB00052418-07; AB00052418_08; AB00052418_09; A832543; Q300989; Q-201294; SR-01000075384-1; SR-01000075384-4; SR-01000075384-6; SR-01000075384-7; (S)-2-Amino-3-(3,4-dihydroxy-phenyl)-propionic acid; F0347-4695; Levodopa, British Pharmacopoeia (BP) Reference Standard; Levodopa, European Pharmacopoeia (EP) Reference Standard; Z1762772338; (2S)-2-amino-3-(3,4-dihydroxyphenyl)propanoic acidL-dopa; UNII-QI9C343R60 component WTDRDQBEARUVNC-LURJTMIESA-N; 1E83F927-C221-46AA-B90A-81B33C5F3868; 3,4-Dihydroxy-L-phenylalanine, Vetec(TM) reagent grade, 98%; Levodopa, United States Pharmacopeia (USP) Reference Standard; 3,4-Dihydroxy-L-phenylalanine, certified reference material, TraceCERT(R); Levodopa, Pharmaceutical Secondary Standard; Certified Reference Material; 122769-74-8; L-Methyldopa ; (2S)-2-Amino-3-(3,4-dihydroxyphenyl)-2-methylpropanoic acid; 3-(3,4-Dihydroxyphenyl)- -methyl-L-alanine; 3-Hydroxy-a-methyl-L-tyrosine
    Click to Show/Hide
Indication
In total 1 Indication(s)
Parkinson disease [ICD-11: 8A00]
Approved
[1]
Structure
Drug Resistance Disease(s)
Disease(s) with Clinically Reported Resistance for This Drug (1 diseases)
Parkinson disease [ICD-11: 8A00]
[1]
Click to Show/Hide the Molecular Information and External Link(s) of This Drug
Formula
C9H11NO4
IsoSMILES
C1=CC(=C(C=C1C[C@@H](C(=O)O)N)O)O
InChI
1S/C9H11NO4/c10-6(9(13)14)3-5-1-2-7(11)8(12)4-5/h1-2,4,6,11-12H,3,10H2,(H,13,14)/t6-/m0/s1
InChIKey
WTDRDQBEARUVNC-LURJTMIESA-N
PubChem CID
6047
TTD Drug ID
D01EZI
VARIDT ID
DR00125
INTEDE ID
DR0939
DrugBank ID
DB01235
Type(s) of Resistant Mechanism of This Drug
  ADTT: Aberration of the Drug's Therapeutic Target
Drug Resistance Data Categorized by Their Corresponding Diseases
ICD-08: Nervous system diseases
Click to Show/Hide the Resistance Disease of This Class
Parkinson disease [ICD-11: 8A00]
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
  Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Key Molecule: Leucine rich repeat kinase 2 (LRRK2) [1]
Resistant Disease Parkinson disease [ICD-11: 8A00.0]
 Disease Info 
Molecule Alteration Missense mutation
p.I2020T
 Molecule Info 
Wild Type Structure Method: Electron microscopy Resolution: 3.05  Å
PDB: 8TXZ
Mutant Type Structure Method: Electron microscopy Resolution: 2.70  Å
PDB: 8TZG
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.18
TM score: 0.95893
Amino acid change:
I2020T
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
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N
R
R
M
M
K
K
L
L
M
M
I
I
1340
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V
V
G
G
N
N
T
T
G
G
S
S
G
G
K
K
T
T
T
T
1350
|
L
L
L
L
Q
Q
Q
Q
L
L
M
M
K
K
T
T
K
K
K
K
1360
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S
S
D
D
L
L
G
G
M
M
Q
Q
S
S
A
A
T
T
V
V
1370
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G
G
I
I
D
D
V
V
K
K
D
D
W
W
P
P
I
I
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1380
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I
I
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R
D
D
K
K
R
R
K
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R
R
D
D
L
L
V
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1390
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L
L
N
N
V
V
W
W
D
D
F
F
A
A
G
G
R
R
E
E
1400
|
E
E
F
F
Y
Y
S
S
T
T
H
H
P
P
H
H
F
F
M
M
1410
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T
T
Q
Q
R
R
A
A
L
L
Y
Y
L
L
A
A
V
V
Y
Y
1420
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D
D
L
L
S
S
K
K
G
G
Q
Q
A
A
E
E
V
V
D
D
1430
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A
A
M
M
K
K
P
P
W
W
L
L
F
F
N
N
I
I
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1440
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A
A
R
R
A
A
S
S
S
S
S
S
P
P
V
V
I
I
L
L
1450
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V
V
G
G
T
T
H
H
L
L
D
D
V
V
S
S
D
D
E
E
1460
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K
K
Q
Q
R
R
K
K
A
A
C
C
M
M
S
S
K
K
I
I
1470
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T
T
K
K
E
E
L
L
L
L
N
N
K
K
R
R
G
G
F
F
1480
|
P
P
A
A
I
I
R
R
D
D
Y
Y
H
H
F
F
V
V
N
N
1490
|
A
A
T
T
E
E
E
E
S
S
D
D
A
A
L
L
A
A
K
K
1500
|
L
L
R
R
K
K
T
T
I
I
I
I
N
N
E
E
S
S
L
L
1510
|
N
N
F
F
K
K
I
I
R
R
D
D
Q
Q
L
L
V
V
V
V
1520
|
G
G
Q
Q
L
L
I
I
P
P
D
D
C
C
Y
Y
V
V
E
E
1530
|
L
L
E
E
K
K
I
I
I
I
L
L
S
S
E
E
R
R
K
K
1540
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N
N
V
V
P
P
I
I
E
E
F
F
P
P
V
V
I
I
D
D
1550
|
R
R
K
K
R
R
L
L
L
L
Q
Q
L
L
V
V
R
R
E
E
1560
|
N
N
Q
Q
L
L
Q
Q
L
L
D
D
E
E
N
N
E
E
L
L
1570
|
P
P
H
H
A
A
V
V
H
H
F
F
L
L
N
N
E
E
S
S
1580
|
G
G
V
V
L
L
L
L
H
H
F
F
Q
Q
D
D
P
P
A
A
1590
|
L
L
Q
Q
L
L
S
S
D
D
L
L
Y
Y
F
F
V
V
E
E
1600
|
P
P
K
K
W
W
L
L
C
C
K
K
I
I
M
M
A
A
Q
Q
1610
|
I
I
L
L
T
T
V
V
K
K
V
V
E
E
G
G
C
C
P
P
1620
|
K
K
H
H
P
P
K
K
G
G
I
I
I
I
S
S
R
R
R
R
1630
|
D
D
V
V
E
E
K
K
F
F
L
L
S
S
K
K
K
K
R
R
1640
|
K
K
F
F
P
P
K
K
N
N
Y
Y
M
M
S
S
Q
Q
Y
Y
1650
|
F
F
K
K
L
L
L
L
E
E
K
K
F
F
Q
Q
I
I
A
A
1660
|
L
L
P
P
I
I
G
G
E
E
E
E
Y
Y
L
L
L
L
V
V
1670
|
P
P
S
S
S
S
L
L
S
S
D
D
H
H
R
R
P
P
V
V
1680
|
I
I
E
E
L
L
P
P
H
H
C
C
E
E
N
N
S
S
E
E
1690
|
I
I
I
I
I
I
R
R
L
L
Y
Y
E
E
M
M
P
P
Y
Y
1700
|
F
F
P
P
M
M
G
G
F
F
W
W
S
S
R
R
L
L
I
I
1710
|
N
N
R
R
L
L
L
L
E
E
I
I
S
S
P
P
Y
Y
M
M
1720
|
L
L
S
S
G
G
R
R
E
E
R
R
A
A
L
L
R
R
P
P
1730
|
N
N
R
R
M
M
Y
Y
W
W
R
R
Q
Q
G
G
I
I
Y
Y
1740
|
L
L
N
N
W
W
S
S
P
P
E
E
A
A
Y
Y
C
C
L
L
1750
|
V
V
G
G
S
S
E
E
V
V
L
L
D
D
N
N
H
H
P
P
1760
|
E
E
S
S
F
F
L
L
K
K
I
I
T
T
V
V
P
P
S
S
1770
|
C
C
R
R
K
K
G
G
C
C
I
I
L
L
L
L
G
G
Q
Q
1780
|
V
V
V
V
D
D
H
H
I
I
D
D
S
S
L
L
M
M
E
E
1790
|
E
E
W
W
F
F
P
P
G
G
L
L
L
L
E
E
I
I
D
D
1800
|
I
I
C
C
G
G
E
E
G
G
E
E
T
T
L
L
L
L
K
K
1810
|
K
K
W
W
A
A
L
L
Y
Y
S
S
F
F
N
N
D
D
G
G
1820
|
E
E
E
E
H
H
Q
Q
K
K
I
I
L
L
L
L
D
D
D
D
1830
|
L
L
M
M
K
K
K
K
A
A
E
E
E
E
G
G
D
D
L
L
1840
|
L
L
V
V
N
N
P
P
D
D
Q
Q
P
P
R
R
L
L
T
T
1850
|
I
I
P
P
I
I
S
S
Q
Q
I
I
A
A
P
P
D
D
L
L
1860
|
I
I
L
L
A
A
D
D
L
L
P
P
R
R
N
N
I
I
M
M
1870
|
L
L
N
N
N
N
D
D
E
E
L
L
E
E
F
F
E
E
Q
Q
1880
|
A
A
P
P
E
E
F
F
L
L
L
L
G
G
D
D
G
G
S
S
1890
|
F
F
G
G
S
S
V
V
Y
Y
R
R
A
A
A
A
Y
Y
E
E
1900
|
G
G
E
E
E
E
V
V
A
A
V
V
K
K
I
I
F
F
N
N
1910
|
K
K
H
H
T
T
S
S
L
L
R
R
L
L
L
L
R
R
Q
Q
1920
|
E
E
L
L
V
V
V
V
L
L
C
C
H
H
L
L
H
H
H
H
1930
|
P
P
S
S
L
L
I
I
S
S
L
L
L
L
A
A
A
A
G
G
1940
|
I
I
R
R
P
P
R
R
M
M
L
L
V
V
M
M
E
E
L
L
1950
|
A
A
S
S
K
K
G
G
S
S
L
L
D
D
R
R
L
L
L
L
1960
|
Q
Q
Q
Q
D
D
K
K
A
A
S
S
L
L
T
T
R
R
T
T
1970
|
L
L
Q
Q
H
H
R
R
I
I
A
A
L
L
H
H
V
V
A
A
1980
|
D
D
G
G
L
L
R
R
Y
Y
L
L
H
H
S
S
A
A
M
M
1990
|
I
I
I
I
Y
Y
R
R
D
D
L
L
K
K
P
P
H
H
N
N
2000
|
V
V
L
L
L
L
F
F
T
T
L
L
Y
Y
P
P
N
N
A
A
2010
|
A
A
I
I
I
I
A
A
K
K
I
I
A
A
D
D
Y
Y
G
G
2020
|
I
T
A
A
Q
Q
Y
Y
C
C
C
C
R
R
M
M
G
G
I
I
2030
|
K
K
T
T
S
S
E
E
G
G
T
T
P
P
G
G
F
F
R
R
2040
|
A
A
P
P
E
E
V
V
A
A
R
R
G
G
N
N
V
V
I
I
2050
|
Y
Y
N
N
Q
Q
Q
Q
A
A
D
D
V
V
Y
Y
S
S
F
F
2060
|
G
G
L
L
L
L
L
L
Y
Y
D
D
I
I
L
L
T
T
T
T
2070
|
G
G
G
G
R
R
I
I
V
V
E
E
G
G
L
L
K
K
F
F
2080
|
P
P
N
N
E
E
F
F
D
D
E
E
L
L
E
E
I
I
Q
Q
2090
|
G
G
K
K
L
L
P
P
D
D
P
P
V
V
K
K
E
E
Y
Y
2100
|
G
G
C
C
A
A
P
P
W
W
P
P
M
M
V
V
E
E
K
K
2110
|
L
L
I
I
K
K
Q
Q
C
C
L
L
K
K
E
E
N
N
P
P
2120
|
Q
Q
E
E
R
R
P
P
T
T
S
S
A
A
Q
Q
V
V
F
F
2130
|
D
D
I
I
L
L
N
N
S
S
A
A
E
E
L
L
V
V
C
C
2140
|
L
L
T
T
R
R
R
R
I
I
L
L
L
L
P
P
K
K
N
N
2150
|
V
V
I
I
V
V
E
E
C
C
M
M
V
V
A
A
T
T
H
H
2160
|
H
H
N
N
S
S
R
R
N
N
A
A
S
S
I
I
W
W
L
L
2170
|
G
G
C
C
G
G
H
H
T
T
D
D
R
R
G
G
Q
Q
L
L
2180
|
S
S
F
F
L
L
D
D
L
L
N
N
T
T
E
E
G
G
Y
Y
2190
|
T
T
S
S
E
E
E
E
V
V
A
A
D
D
S
S
R
R
I
I
2200
|
L
L
C
C
L
L
A
A
L
L
V
V
H
H
L
L
P
P
V
V
2210
|
E
E
K
K
E
E
S
S
W
W
I
I
V
V
S
S
G
G
T
T
2220
|
Q
Q
S
S
G
G
T
T
L
L
L
L
V
V
I
I
N
N
T
T
2230
|
E
E
D
D
G
G
K
K
K
K
R
R
H
H
T
T
L
L
E
E
2240
|
K
K
M
M
T
T
D
D
S
S
V
V
T
T
C
C
L
L
Y
Y
2250
|
C
C
N
N
S
S
F
F
S
S
K
K
Q
Q
S
S
K
K
Q
Q
2260
|
K
K
N
N
F
F
L
L
L
L
V
V
G
G
T
T
A
A
D
D
2270
|
G
G
K
K
L
L
A
A
I
I
F
F
E
E
D
D
K
K
T
T
2280
|
V
V
K
K
L
L
K
K
G
G
A
A
A
A
P
P
L
L
K
K
2290
|
I
I
L
L
N
N
I
I
G
G
N
N
V
V
S
S
T
T
P
P
2300
|
L
L
M
M
C
C
L
L
S
S
E
E
S
S
T
T
N
N
S
S
2310
|
T
T
E
E
R
R
N
N
V
V
M
M
W
W
G
G
G
G
C
C
2320
|
G
G
T
T
K
K
I
I
F
F
S
S
F
F
S
S
N
N
D
D
2330
|
F
F
T
T
I
I
Q
Q
K
K
L
L
I
I
E
E
T
T
R
R
2340
|
T
T
S
S
Q
Q
L
L
F
F
S
S
Y
Y
A
A
A
A
F
F
2350
|
S
S
D
D
S
S
N
N
I
I
I
I
T
T
V
V
V
V
V
V
2360
|
D
D
T
T
A
A
L
L
Y
Y
I
I
A
A
K
K
Q
Q
N
N
2370
|
S
S
P
P
V
V
V
V
E
E
V
V
W
W
D
D
K
K
K
K
2380
|
T
T
E
E
K
K
L
L
C
C
G
G
L
L
I
I
D
D
C
C
2390
|
V
V
H
H
F
F
L
L
R
R
E
E
V
V
M
M
V
V
K
K
2400
|
E
E
N
N
K
K
E
E
S
S
K
K
H
H
K
K
M
M
S
S
2410
|
Y
Y
S
S
G
G
R
R
V
V
K
K
T
T
L
L
C
C
L
L
2420
|
Q
Q
K
K
N
N
T
T
A
A
L
L
W
W
I
I
G
G
T
T
2430
|
G
G
G
G
G
G
H
H
I
I
L
L
L
L
L
L
D
D
L
L
2440
|
S
S
T
T
R
R
R
R
L
L
I
I
R
R
V
V
I
I
Y
Y
2450
|
N
N
F
F
C
C
N
N
S
S
V
V
R
R
V
V
M
M
M
M
2460
|
T
T
A
A
Q
Q
L
L
G
G
S
S
L
L
K
K
N
N
V
V
2470
|
M
M
L
L
V
V
L
L
G
G
Y
Y
N
N
R
R
K
K
N
N
2480
|
T
T
E
E
G
G
T
T
Q
Q
K
K
Q
Q
K
K
E
E
I
I
2490
|
Q
Q
S
S
C
C
L
L
T
T
V
V
W
W
D
D
I
I
N
N
2500
|
L
L
P
P
H
H
E
E
V
V
Q
Q
N
N
L
L
E
E
K
K
2510
|
H
H
I
I
E
E
V
V
R
R
K
K
E
E
L
L
A
A
E
E
2520
|
K
K
M
M
R
R
R
-
T
-
S
-
V
-
E
-
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
Experiment for
Drug Resistance		 Molecular docking analysis; Molecular dynamic simulation assay
Mechanism Description The deleterious mutations G2019S and I2020T in the kinase domain were playing a key role in causing resistance to drug levedopa.
Key Molecule: Leucine rich repeat kinase 2 (LRRK2) [1]
Resistant Disease Parkinson disease [ICD-11: 8A00.0]
 Disease Info 
Molecule Alteration Missense mutation
p.G2019S
 Molecule Info 
Wild Type Structure Method: Electron microscopy Resolution: 3.05  Å
PDB: 8TXZ
Mutant Type Structure Method: Electron microscopy Resolution: 2.70  Å
PDB: 8TZC
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.27
TM score: 0.89948
Amino acid change:
G2019S
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
-
N
R
R
M
M
K
K
L
L
M
M
I
I
1340
|
V
V
G
G
N
N
T
T
G
G
S
S
G
G
K
K
T
T
T
T
1350
|
L
L
L
L
Q
Q
Q
Q
L
L
M
M
K
K
T
T
K
K
K
K
1360
|
S
S
D
D
L
L
G
G
M
M
Q
Q
S
S
A
A
T
T
V
V
1370
|
G
G
I
I
D
D
V
V
K
K
D
D
W
W
P
P
I
I
Q
Q
1380
|
I
I
R
R
D
D
K
K
R
R
K
K
R
R
D
D
L
L
V
V
1390
|
L
L
N
N
V
V
W
W
D
D
F
F
A
A
G
G
R
R
E
E
1400
|
E
E
F
F
Y
Y
S
S
T
T
H
H
P
P
H
H
F
F
M
M
1410
|
T
T
Q
Q
R
R
A
A
L
L
Y
Y
L
L
A
A
V
V
Y
Y
1420
|
D
D
L
L
S
S
K
K
G
G
Q
Q
A
A
E
E
V
V
D
D
1430
|
A
A
M
M
K
K
P
P
W
W
L
L
F
F
N
N
I
I
K
K
1440
|
A
A
R
R
A
A
S
S
S
S
S
S
P
P
V
V
I
I
L
L
1450
|
V
V
G
G
T
T
H
H
L
L
D
D
V
V
S
S
D
D
E
E
1460
|
K
K
Q
Q
R
R
K
K
A
A
C
C
M
M
S
S
K
K
I
I
1470
|
T
T
K
K
E
E
L
L
L
L
N
N
K
K
R
R
G
G
F
F
1480
|
P
P
A
A
I
I
R
R
D
D
Y
Y
H
H
F
F
V
V
N
N
1490
|
A
A
T
T
E
E
E
E
S
S
D
D
A
A
L
L
A
A
K
K
1500
|
L
L
R
R
K
K
T
T
I
I
I
I
N
N
E
E
S
S
L
L
1510
|
N
N
F
F
K
K
I
I
R
R
D
D
Q
Q
L
L
V
V
V
V
1520
|
G
G
Q
Q
L
L
I
I
P
P
D
D
C
C
Y
Y
V
V
E
E
1530
|
L
L
E
E
K
K
I
I
I
I
L
L
S
S
E
E
R
R
K
K
1540
|
N
N
V
V
P
P
I
I
E
E
F
F
P
P
V
V
I
I
D
D
1550
|
R
R
K
K
R
R
L
L
L
L
Q
Q
L
L
V
V
R
R
E
E
1560
|
N
N
Q
Q
L
L
Q
Q
L
L
D
D
E
E
N
N
E
E
L
L
1570
|
P
P
H
H
A
A
V
V
H
H
F
F
L
L
N
N
E
E
S
S
1580
|
G
G
V
V
L
L
L
L
H
H
F
F
Q
Q
D
D
P
P
A
A
1590
|
L
L
Q
Q
L
L
S
S
D
D
L
L
Y
Y
F
F
V
V
E
E
1600
|
P
P
K
K
W
W
L
L
C
C
K
K
I
I
M
M
A
A
Q
Q
1610
|
I
I
L
L
T
T
V
V
K
K
V
V
E
E
G
G
C
C
P
P
1620
|
K
K
H
H
P
P
K
K
G
G
I
I
I
I
S
S
R
R
R
R
1630
|
D
D
V
V
E
E
K
K
F
F
L
L
S
S
K
K
K
K
R
R
1640
|
K
K
F
F
P
P
K
K
N
N
Y
Y
M
M
S
S
Q
Q
Y
Y
1650
|
F
F
K
K
L
L
L
L
E
E
K
K
F
F
Q
Q
I
I
A
A
1660
|
L
L
P
P
I
I
G
G
E
E
E
E
Y
Y
L
L
L
L
V
V
1670
|
P
P
S
S
S
S
L
L
S
S
D
D
H
H
R
R
P
P
V
V
1680
|
I
I
E
E
L
L
P
P
H
H
C
C
E
E
N
N
S
S
E
E
1690
|
I
I
I
I
I
I
R
R
L
L
Y
Y
E
E
M
M
P
P
Y
Y
1700
|
F
F
P
P
M
M
G
G
F
F
W
W
S
S
R
R
L
L
I
I
1710
|
N
N
R
R
L
L
L
L
E
E
I
I
S
S
P
P
Y
Y
M
M
1720
|
L
L
S
S
G
G
R
R
E
E
R
R
A
A
L
L
R
R
P
P
1730
|
N
N
R
R
M
M
Y
Y
W
W
R
R
Q
Q
G
G
I
I
Y
Y
1740
|
L
L
N
N
W
W
S
S
P
P
E
E
A
A
Y
Y
C
C
L
L
1750
|
V
V
G
G
S
S
E
E
V
V
L
L
D
D
N
N
H
H
P
P
1760
|
E
E
S
S
F
F
L
L
K
K
I
I
T
T
V
V
P
P
S
S
1770
|
C
C
R
R
K
K
G
G
C
C
I
I
L
L
L
L
G
G
Q
Q
1780
|
V
V
V
V
D
D
H
H
I
I
D
D
S
S
L
L
M
M
E
E
1790
|
E
E
W
W
F
F
P
P
G
G
L
L
L
L
E
E
I
I
D
D
1800
|
I
I
C
C
G
G
E
E
G
G
E
E
T
T
L
L
L
L
K
K
1810
|
K
K
W
W
A
A
L
L
Y
Y
S
S
F
F
N
N
D
D
G
G
1820
|
E
E
E
E
H
H
Q
Q
K
K
I
I
L
L
L
L
D
D
D
D
1830
|
L
L
M
M
K
K
K
K
A
A
E
E
E
E
G
G
D
D
L
L
1840
|
L
L
V
V
N
N
P
P
D
D
Q
Q
P
P
R
R
L
L
T
T
1850
|
I
I
P
P
I
I
S
S
Q
Q
I
I
A
A
P
P
D
D
L
L
1860
|
I
I
L
L
A
A
D
D
L
L
P
P
R
R
N
N
I
I
M
M
1870
|
L
L
N
N
N
N
D
D
E
E
L
L
E
E
F
F
E
E
Q
Q
1880
|
A
A
P
P
E
E
F
F
L
L
L
L
G
G
D
D
G
G
S
S
1890
|
F
F
G
G
S
S
V
V
Y
Y
R
R
A
A
A
A
Y
Y
E
E
1900
|
G
G
E
E
E
E
V
V
A
A
V
V
K
K
I
I
F
F
N
N
1910
|
K
K
H
H
T
T
S
S
L
L
R
R
L
L
L
L
R
R
Q
Q
1920
|
E
E
L
L
V
V
V
V
L
L
C
C
H
H
L
L
H
H
H
H
1930
|
P
P
S
S
L
L
I
I
S
S
L
L
L
L
A
A
A
A
G
G
1940
|
I
I
R
R
P
P
R
R
M
M
L
L
V
V
M
M
E
E
L
L
1950
|
A
A
S
S
K
K
G
G
S
S
L
L
D
D
R
R
L
L
L
L
1960
|
Q
Q
Q
Q
D
D
K
K
A
A
S
S
L
L
T
T
R
R
T
T
1970
|
L
L
Q
Q
H
H
R
R
I
I
A
A
L
L
H
H
V
V
A
A
1980
|
D
D
G
G
L
L
R
R
Y
Y
L
L
H
H
S
S
A
A
M
M
1990
|
I
I
I
I
Y
Y
R
R
D
D
L
L
K
K
P
P
H
H
N
N
2000
|
V
V
L
L
L
L
F
F
T
T
L
L
Y
Y
P
P
N
N
A
A
2010
|
A
A
I
I
I
I
A
A
K
K
I
I
A
A
D
D
Y
Y
G
S
2020
|
I
I
A
A
Q
Q
Y
Y
C
C
C
C
R
R
M
M
G
G
I
I
2030
|
K
K
T
T
S
S
E
E
G
G
T
T
P
P
G
G
F
F
R
R
2040
|
A
A
P
P
E
E
V
V
A
A
R
R
G
G
N
N
V
V
I
I
2050
|
Y
Y
N
N
Q
Q
Q
Q
A
A
D
D
V
V
Y
Y
S
S
F
F
2060
|
G
G
L
L
L
L
L
L
Y
Y
D
D
I
I
L
L
T
T
T
T
2070
|
G
G
G
G
R
R
I
I
V
V
E
E
G
G
L
L
K
K
F
F
2080
|
P
P
N
N
E
E
F
F
D
D
E
E
L
L
E
E
I
I
Q
Q
2090
|
G
G
K
K
L
L
P
P
D
D
P
P
V
V
K
K
E
E
Y
Y
2100
|
G
G
C
C
A
A
P
P
W
W
P
P
M
M
V
V
E
E
K
K
2110
|
L
L
I
I
K
K
Q
Q
C
C
L
L
K
K
E
E
N
N
P
P
2120
|
Q
Q
E
E
R
R
P
P
T
T
S
S
A
A
Q
Q
V
V
F
F
2130
|
D
D
I
I
L
L
N
N
S
S
A
A
E
E
L
L
V
V
C
C
2140
|
L
L
T
T
R
R
R
R
I
I
L
L
L
L
P
P
K
K
N
N
2150
|
V
V
I
I
V
V
E
E
C
C
M
M
V
V
A
A
T
T
H
H
2160
|
H
H
N
N
S
S
R
R
N
N
A
A
S
S
I
I
W
W
L
L
2170
|
G
G
C
C
G
G
H
H
T
T
D
D
R
R
G
G
Q
Q
L
L
2180
|
S
S
F
F
L
L
D
D
L
L
N
N
T
T
E
E
G
G
Y
Y
2190
|
T
T
S
S
E
E
E
E
V
V
A
A
D
D
S
S
R
R
I
I
2200
|
L
L
C
C
L
L
A
A
L
L
V
V
H
H
L
L
P
P
V
V
2210
|
E
E
K
K
E
E
S
S
W
W
I
I
V
V
S
S
G
G
T
T
2220
|
Q
Q
S
S
G
G
T
T
L
L
L
L
V
V
I
I
N
N
T
T
2230
|
E
E
D
D
G
G
K
K
K
K
R
R
H
H
T
T
L
L
E
E
2240
|
K
K
M
M
T
T
D
D
S
S
V
V
T
T
C
C
L
L
Y
Y
2250
|
C
C
N
N
S
S
F
F
S
S
K
K
Q
Q
S
S
K
K
Q
Q
2260
|
K
K
N
N
F
F
L
L
L
L
V
V
G
G
T
T
A
A
D
D
2270
|
G
G
K
K
L
L
A
A
I
I
F
F
E
E
D
D
K
K
T
T
2280
|
V
V
K
K
L
L
K
K
G
G
A
A
A
A
P
P
L
L
K
K
2290
|
I
I
L
L
N
N
I
I
G
G
N
N
V
V
S
S
T
T
P
P
2300
|
L
L
M
M
C
C
L
L
S
S
E
E
S
S
T
T
N
N
S
S
2310
|
T
T
E
E
R
R
N
N
V
V
M
M
W
W
G
G
G
G
C
C
2320
|
G
G
T
T
K
K
I
I
F
F
S
S
F
F
S
S
N
N
D
D
2330
|
F
F
T
T
I
I
Q
Q
K
K
L
L
I
I
E
E
T
T
R
R
2340
|
T
T
S
S
Q
Q
L
L
F
F
S
S
Y
Y
A
A
A
A
F
F
2350
|
S
S
D
D
S
S
N
N
I
I
I
I
T
T
V
V
V
V
V
V
2360
|
D
D
T
T
A
A
L
L
Y
Y
I
I
A
A
K
K
Q
Q
N
N
2370
|
S
S
P
P
V
V
V
V
E
E
V
V
W
W
D
D
K
K
K
K
2380
|
T
T
E
E
K
K
L
L
C
C
G
G
L
L
I
I
D
D
C
C
2390
|
V
V
H
H
F
F
L
L
R
R
E
E
V
V
M
M
V
V
K
K
2400
|
E
E
N
N
K
K
E
E
S
S
K
K
H
H
K
K
M
M
S
S
2410
|
Y
Y
S
S
G
G
R
R
V
V
K
K
T
T
L
L
C
C
L
L
2420
|
Q
Q
K
K
N
N
T
T
A
A
L
L
W
W
I
I
G
G
T
T
2430
|
G
G
G
G
G
G
H
H
I
I
L
L
L
L
L
L
D
D
L
L
2440
|
S
S
T
T
R
R
R
R
L
L
I
I
R
R
V
V
I
I
Y
Y
2450
|
N
N
F
F
C
C
N
N
S
S
V
V
R
R
V
V
M
M
M
M
2460
|
T
T
A
A
Q
Q
L
L
G
G
S
S
L
L
K
K
N
N
V
V
2470
|
M
M
L
L
V
V
L
L
G
G
Y
Y
N
N
R
R
K
K
N
N
2480
|
T
T
E
E
G
G
T
T
Q
Q
K
K
Q
Q
K
K
E
E
I
I
2490
|
Q
Q
S
S
C
C
L
L
T
T
V
V
W
W
D
D
I
I
N
N
2500
|
L
L
P
P
H
H
E
E
V
V
Q
Q
N
N
L
L
E
E
K
K
2510
|
H
H
I
I
E
E
V
V
R
R
K
K
E
E
L
L
A
A
E
E
2520
|
K
K
M
M
R
R
R
R
T
T
S
S
V
V
E
E
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
Experiment for
Drug Resistance		 Molecular docking analysis; Molecular dynamic simulation assay
Mechanism Description The deleterious mutations G2019S and I2020T in the kinase domain were playing a key role in causing resistance to drug levedopa.
References
Ref 1 Exploring the functional impact of mutational drift in LRRK2 gene and identification of specific inhibitors for the treatment of Parkinson disease .J Cell Biochem. 2018 Jun;119(6):4878-4889. doi: 10.1002/jcb.26703. Epub 2018 Mar 9. 10.1002/jcb.26703

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