PDBsum entry 3d1t

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Hydrolase, biosynthetic protein PDB id
Protein chains
244 a.a. *
_ZN ×2
Waters ×133
* Residue conservation analysis
PDB id:
Name: Hydrolase, biosynthetic protein
Title: Crystal structure of gcyh-ib
Structure: Upf0343 protein ngo0387. Chain: a, b. Engineered: yes
Source: Neisseria gonorrhoeae. Organism_taxid: 485. Atcc: 700825. Gene: ngo0387. Expressed in: escherichia coli. Expression_system_taxid: 562.
2.20Å     R-factor:   0.200     R-free:   0.250
Authors: B.Sankaran,M.A.Swairjo
Key ref: B.Sankaran et al. (2009). Zinc-independent folate biosynthesis: genetic, biochemical, and structural investigations reveal new metal dependence for GTP cyclohydrolase IB. J Bacteriol, 191, 6936-6949. PubMed id: 19767425
06-May-08     Release date:   12-May-09    
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Protein chains
Pfam   ArchSchema ?
Q5F9K6  (GCH4_NEIG1) -  GTP cyclohydrolase FolE2
257 a.a.
244 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - Gtp cyclohydrolase i.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

Folate Biosynthesis (early stages)
      Reaction: GTP + H2O = formate + 2-amino-4-hydroxy-6-(erythro-1,2,3- trihydroxypropyl)-dihydropteridine triphosphate
+ H(2)O
Bound ligand (Het Group name = ACY)
matches with 75.00% similarity
+ 2-amino-4-hydroxy-6-(erythro-1,2,3- trihydroxypropyl)-dihydropteridine triphosphate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     7,8-dihydroneopterin 3'-triphosphate biosynthetic process   1 term 
  Biochemical function     hydrolase activity     3 terms  


    Added reference    
J Bacteriol 191:6936-6949 (2009)
PubMed id: 19767425  
Zinc-independent folate biosynthesis: genetic, biochemical, and structural investigations reveal new metal dependence for GTP cyclohydrolase IB.
B.Sankaran, S.A.Bonnett, K.Shah, S.Gabriel, R.Reddy, P.Schimmel, D.A.Rodionov, Crécy-Lagard, J.D.Helmann, D.Iwata-Reuyl, M.A.Swairjo.
GTP cyclohydrolase I (GCYH-I) is an essential Zn(2+)-dependent enzyme that catalyzes the first step of the de novo folate biosynthetic pathway in bacteria and plants, the 7-deazapurine biosynthetic pathway in Bacteria and Archaea, and the biopterin pathway in mammals. We recently reported the discovery of a new prokaryotic-specific GCYH-I (GCYH-IB) that displays no sequence identity to the canonical enzyme and is present in approximately 25% of bacteria, the majority of which lack the canonical GCYH-I (renamed GCYH-IA). Genomic and genetic analyses indicate that in those organisms possessing both enzymes, e.g., Bacillus subtilis, GCYH-IA and -IB are functionally redundant, but differentially expressed. Whereas GCYH-IA is constitutively expressed, GCYH-IB is expressed only under Zn(2+)-limiting conditions. These observations are consistent with the hypothesis that GCYH-IB functions to allow folate biosynthesis during Zn(2+) starvation. Here, we present biochemical and structural data showing that bacterial GCYH-IB, like GCYH-IA, belongs to the tunneling-fold (T-fold) superfamily. However, the GCYH-IA and -IB enzymes exhibit significant differences in global structure and active-site architecture. While GCYH-IA is a unimodular, homodecameric, Zn(2+)-dependent enzyme, GCYH-IB is a bimodular, homotetrameric enzyme activated by a variety of divalent cations. The structure of GCYH-IB and the broad metal dependence exhibited by this enzyme further underscore the mechanistic plasticity that is emerging for the T-fold superfamily. Notably, while humans possess the canonical GCYH-IA enzyme, many clinically important human pathogens possess only the GCYH-IB enzyme, suggesting that this enzyme is a potential new molecular target for antibacterial development.

Literature references that cite this PDB file's key reference

  PubMed id Reference
21255113 C.E.Blaby-Haas, R.Furman, D.A.Rodionov, I.Artsimovitch, and Crécy-Lagard (2011).
Role of a Zn-independent DksA in Zn homeostasis and stringent response.
  Mol Microbiol, 79, 700-715.  
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