Molecule Information

General Information of the Molecule (ID: Mol01037)

• Name: Penicillin-binding protein 1A (PBP1A) ,Neisseria gonorrhoeae
• Synonyms: PBP-1a; PBP1a; Peptidoglycan TGase; DD-transpeptidase; ponA
• Molecule Type: Protein
• Gene Name: mrcA
• Sequence:
  MIKKILTTCFGLFFGFCVFGVGLVAIAILVTYPKLPSLDSLQHYQPKMPLTIYSADGEVI
  GMYGEQRREFTKIGDFPEVLRNAVIAAEDKRFYRHWGVDVWGVARAAVGNVVSGSVQSGA
  STITQQVAKNFYLSSEKTFTRKFNEVLLAYKIEQSLSKDKILELYFNQIYLGQRAYGFAS
  AAQIYFNKNVRDLTLAEAAMLAGLPKAPSAYNPIVNPERAKLRQKYILNNMLEEKMITVQ
  QRDQALNEELHYERFVRKIDQSALYVAEMVRRELYEKYGEDAYTQGFKVYTTVRTDHQKA
  ATEALRKALRNFDRGSSYRGAENYIDLSKSEDVEETVSQYLSGLYTVDKMVPAVVLDVTK
  KKNVVIQLPGGRRVALDRRALGFAARAVDNEKMGEDRIRRGAVIRVKNNGGRWAVVQEPL
  LQGALVSLDAKTGAVRALVGGYDFHSKTFNRAVQAMRQPGSTFKPFVYSAALSKGMTAST
  VVNDAPISLPGKGPNGSVWTPKNSDGRYSGYITLRQALTASKNMVSIRILMSIGVGYAQQ
  YIRRFGFRPSELPASLSMALGTGETTPLKVAEAYSVFANGGYRVSSHVIDKIYDRDGRLR
  AQMQPLVAGQNAPQAIDPRNAYIMYKIMQDVVRVGTARGAAALGRTDIAGKTGTTNDNKD
  AWFVGFNPDVVTAVYIGFDKPKSMGRAGYGGTIAVPVWVDYMRFALKGKQGKGMKMPEGV
  VSSNGEYYMKERMVTDPGLMLDNSGIAPQPSRRAKEDDEAAVENEQQGRSDETRQDVQET
  PVLPSNTDSKQQQLDSLF
• Function: Cell wall formation. Synthesis of cross-linked peptidoglycan from the lipid intermediates. The enzyme has a penicillin-insensitive transglycosylase N-terminal domain (formation of linear glycan strands) and a penicillin-sensitive transpeptidase C-terminal domain (cross-linking of the peptide subunits). Essential for cell wall synthesis.
• Uniprot ID: PBPA_NEIGO

Kingdom: N.A.
Phylum: Proteobacteria
Class: Betaproteobacteria
Order: Neisseriales
Family: Neisseriaceae
Genus: Neisseria
Species: Neisseria gonorrhoeae

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) 1 drug(s) in total

Penicillin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Gonococcal infection [1]

• Resistant Disease: Gonococcal infection [ICD-11: 1A70.0]
• Resistant Drug: Penicillin
• Molecule Alteration: Missense mutation; p.L421P
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Neisseria gonorrhoeae 0387; 485
• In Vitro Model: Neisseria gonorrhoeae 2227; 485
• In Vitro Model: Neisseria gonorrhoeae 3391; 485
• In Vitro Model: Neisseria gonorrhoeae 5611; 485
• In Vitro Model: Neisseria gonorrhoeae 9634; 485
• Experiment for Molecule Alteration: PCR
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: The ponA1 gene encodes PBP 1 containing a single amino acid mutation, Leu-421-Pro. This single amino acid mutation was present in all chromosomally mediated resistant N. gonorrhoeae (CMRNG) strains for which MICs of penicillin were >=1 ug/ml. PBP 1 harboring this point mutation (PBP 1*) had a three- to fourfold lower rate of acylation (k2/k') than wild-type PBP 1 with a variety of Beta-lactam antibiotics.

References

• Ref 1: Mutations in ponA, the gene encoding penicillin-binding protein 1, and a novel locus, penC, are required for high-level chromosomally mediated penicillin resistance in Neisseria gonorrhoeae. Antimicrob Agents Chemother. 2002 Mar;46(3):769-77. doi: 10.1128/AAC.46.3.769-777.2002.