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PDBsum entry 1fbx

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protein metals Protein-protein interface(s) links
Hydrolase PDB id
1fbx
Jmol
Contents
Protein chains
(+ 9 more) 221 a.a. *
Metals
_CL ×15
_ZN ×15
Waters ×15
* Residue conservation analysis
PDB id:
1fbx
Name: Hydrolase
Title: Crystal structure of zinc-containing e.Coli gtp cyclohydrolase i
Structure: Gtp cyclohydrolase i. Chain: a, b, c, d, e, f, g, h, i, j, k, l, m, n, o. Synonym: gtp-ch-i. Engineered: yes
Source: Escherichia coli. Organism_taxid: 562. Expressed in: escherichia coli. Expression_system_taxid: 562. Other_details: escherichia coli
Biol. unit: Decamer (from PDB file)
Resolution:
2.80Å     R-factor:   0.202     R-free:   0.251
Authors: G.Auerbach,A.Herrmann,A.Bracher,A.Bader,M.Gutlich,M.Fischer, M.Neukamm,H.Nar,M.Garrido-Franco,J.Richardson,R.Huber, A.Bacher
Key ref:
G.Auerbach et al. (2000). Zinc plays a key role in human and bacterial GTP cyclohydrolase I. Proc Natl Acad Sci U S A, 97, 13567-13572. PubMed id: 11087827 DOI: 10.1073/pnas.240463497
Date:
17-Jul-00     Release date:   14-Feb-01    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P0A6T5  (GCH1_ECOLI) -  GTP cyclohydrolase 1
Seq:
Struc:
222 a.a.
221 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.3.5.4.16  - Gtp cyclohydrolase i.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

      Pathway:
Folate Biosynthesis (early stages)
      Reaction: GTP + H2O = formate + 2-amino-4-hydroxy-6-(erythro-1,2,3- trihydroxypropyl)-dihydropteridine triphosphate
GTP
+ H(2)O
= formate
+ 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!
  Cellular component     protein complex   2 terms 
  Biological process     metabolic process   6 terms 
  Biochemical function     catalytic activity     7 terms  

 

 
    Added reference    
 
 
DOI no: 10.1073/pnas.240463497 Proc Natl Acad Sci U S A 97:13567-13572 (2000)
PubMed id: 11087827  
 
 
Zinc plays a key role in human and bacterial GTP cyclohydrolase I.
G.Auerbach, A.Herrmann, A.Bracher, G.Bader, M.Gutlich, M.Fischer, M.Neukamm, M.Garrido-Franco, J.Richardson, H.Nar, R.Huber, A.Bacher.
 
  ABSTRACT  
 
The crystal structure of recombinant human GTP cyclohydrolase I was solved by Patterson search methods by using the coordinates of the Escherichia coli enzyme as a model. The human as well as bacterial enzyme were shown to contain an essential zinc ion coordinated to a His side chain and two thiol groups in each active site of the homodecameric enzymes that had escaped detection during earlier studies of the E. coli enzyme. The zinc ion is proposed to generate a hydroxyl nucleophile for attack of imidazole ring carbon atom eight of the substrate, GTP. It may also be involved in the hydrolytic release of formate from the intermediate, 2-amino-5-formylamino-6-ribosylamino-4(3H)-pyrimidinone 5'-triphosphate, and in the consecutive Amadori rearrangement of the ribosyl moiety.
 
  Selected figure(s)  
 
Figure 1.
Fig. 1. Stereo view of the active site of (a) hGTP-CH-I and (b) eGTP-CH-I harboring zinc. The averaged 2F[o] F[c] electron density maps are shown in blue.
Figure 4.
Fig. 4. Hypothetical reaction mechanism for GTP-CH-I.
 
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19634988 M.A.Wouters, S.W.Fan, and N.L.Haworth (2010).
Disulfides as redox switches: from molecular mechanisms to functional significance.
  Antioxid Redox Signal, 12, 53-91.  
19767425 B.Sankaran, S.A.Bonnett, K.Shah, S.Gabriel, R.Reddy, P.Schimmel, D.A.Rodionov, V.de Crécy-Lagard, J.D.Helmann, D.Iwata-Reuyl, and M.A.Swairjo (2009).
Zinc-independent folate biosynthesis: genetic, biochemical, and structural investigations reveal new metal dependence for GTP cyclohydrolase IB.
  J Bacteriol, 191, 6936-6949.
PDB codes: 3d1t 3d2o
19103603 M.J.Bailey, S.L.Coon, D.A.Carter, A.Humphries, J.S.Kim, Q.Shi, P.Gaildrat, F.Morin, S.Ganguly, J.B.Hogenesch, J.L.Weller, M.F.Rath, M.Møller, R.Baler, D.Sugden, Z.G.Rangel, P.J.Munson, and D.C.Klein (2009).
Night/Day Changes in Pineal Expression of >600 Genes: CENTRAL ROLE OF ADRENERGIC/cAMP SIGNALING.
  J Biol Chem, 284, 7606-7622.  
19598234 S.W.Fan, R.A.George, N.L.Haworth, L.L.Feng, J.Y.Liu, and M.A.Wouters (2009).
Conformational changes in redox pairs of protein structures.
  Protein Sci, 18, 1745-1765.  
18721750 R.M.McCarty, and V.Bandarian (2008).
Deciphering deazapurine biosynthesis: pathway for pyrrolopyrimidine nucleosides toyocamycin and sangivamycin.
  Chem Biol, 15, 790-798.  
17410324 A.De Rosa, C.Carducci, I.Antonozzi, T.Giovanniello, E.Xhoxhi, C.Criscuolo, V.Menchise, S.Striano, A.Filla, and G.De Michele (2007).
A novel mutation in GCH-1 gene in a case of dopa-responsive dystonia.
  J Neurol, 254, 1133-1134.  
16359320 G.V.Mukamolova, A.G.Murzin, E.G.Salina, G.R.Demina, D.B.Kell, A.S.Kaprelyants, and M.Young (2006).
Muralytic activity of Micrococcus luteus Rpf and its relationship to physiological activity in promoting bacterial growth and resuscitation.
  Mol Microbiol, 59, 84-98.  
16696853 L.Swick, and G.Kapatos (2006).
A yeast 2-hybrid analysis of human GTP cyclohydrolase I protein interactions.
  J Neurochem, 97, 1447-1455.  
16360951 R.Futahashi, and H.Fujiwara (2006).
Expression of one isoform of GTP cyclohydrolase I coincides with the larval black markings of the swallowtail butterfly, Papilio xuthus.
  Insect Biochem Mol Biol, 36, 63-70.  
15981250 A.Berchanski, D.Segal, and M.Eisenstein (2005).
Modeling oligomers with Cn or Dn symmetry: application to CAPRI target 10.
  Proteins, 60, 202-206.  
15613396 B.Pierce, W.Tong, and Z.Weng (2005).
M-ZDOCK: a grid-based approach for Cn symmetric multimer docking.
  Bioinformatics, 21, 1472-1478.  
16010344 M.Fischer, and A.Bacher (2005).
Biosynthesis of flavocoenzymes.
  Nat Prod Rep, 22, 324-350.  
15767583 S.G.Van Lanen, J.S.Reader, M.A.Swairjo, V.de Crécy-Lagard, B.Lee, and D.Iwata-Reuyl (2005).
From cyclohydrolase to oxidoreductase: discovery of nitrile reductase activity in a common fold.
  Proc Natl Acad Sci U S A, 102, 4264-4269.  
14717702 T.Suzuki, H.Kurita, and H.Ichinose (2004).
GTP cyclohydrolase I utilizes metal-free GTP as its substrate.
  Eur J Biochem, 271, 349-355.  
14660404 A.He, and J.P.Rosazza (2003).
GTP cyclohydrolase I: purification, characterization, and effects of inhibition on nitric oxide synthase in nocardia species.
  Appl Environ Microbiol, 69, 7507-7513.  
12111724 A.Bermingham, and J.P.Derrick (2002).
The folic acid biosynthesis pathway in bacteria: evaluation of potential for antibacterial drug discovery.
  Bioessays, 24, 637-648.  
12221287 G.Basset, E.P.Quinlivan, M.J.Ziemak, R.Diaz De La Garza, M.Fischer, S.Schiffmann, A.Bacher, J.F.Gregory, and A.D.Hanson (2002).
Folate synthesis in plants: the first step of the pterin branch is mediated by a unique bimodular GTP cyclohydrolase I.
  Proc Natl Acad Sci U S A, 99, 12489-12494.  
12392559 J.Kaiser, N.Schramek, S.Eberhardt, S.Püttmer, M.Schuster, and A.Bacher (2002).
Biosynthesis of vitamin B2.
  Eur J Biochem, 269, 5264-5270.  
11818540 N.Maita, K.Okada, K.Hatakeyama, and T.Hakoshima (2002).
Crystal structure of the stimulatory complex of GTP cyclohydrolase I and its feedback regulatory protein GFRP.
  Proc Natl Acad Sci U S A, 99, 1212-1217.
PDB codes: 1is7 1is8
11575773 H.Sigel, E.M.Bianchi, N.A.Corfù, Y.Kinjo, R.Tribolet, and R.B.Martin (2001).
Stabilities and isomeric equilibria in solutions of monomeric metal-ion complexes of guanosine 5'-triphosphate (GTP4-) and inosine 5'-triphosphate (ITP4-) in comparison with those of adenosine 5'-triphosphate (ATP4-).
  Chemistry, 7, 3729-3737.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.