PDBsum entry 1is7

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protein ligands metals Protein-protein interface(s) links
Hydrolase/protein binding PDB id
Protein chains
(+ 4 more) 194 a.a. *
(+ 4 more) 84 a.a. *
PHE ×10
__K ×10
Waters ×125
* Residue conservation analysis
PDB id:
Name: Hydrolase/protein binding
Title: Crystal structure of rat gtpchi/gfrp stimulatory complex
Structure: Gtp cyclohydrolase i. Chain: a, b, c, d, e, f, g, h, i, j. Engineered: yes. Gtp cyclohydrolase i feedback regulatory protein. Chain: k, l, m, n, o, p, q, r, s, t. Engineered: yes
Source: Rattus norvegicus. Norway rat. Organism_taxid: 10116. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: 20mer (from PQS)
2.80Å     R-factor:   0.228     R-free:   0.264
Authors: N.Maita,K.Okada,K.Hatakeyama,T.Hakoshima
Key ref:
N.Maita et al. (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. PubMed id: 11818540 DOI: 10.1073/pnas.022646999
18-Nov-01     Release date:   20-Feb-02    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P22288  (GCH1_RAT) -  GTP cyclohydrolase 1
241 a.a.
194 a.a.
Protein chains
Pfam   ArchSchema ?
P70552  (GFRP_RAT) -  GTP cyclohydrolase 1 feedback regulatory protein
84 a.a.
84 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: Chains A, B, C, D, E, F, G, H, I, J: 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
= 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   10 terms 
  Biological process     metabolic process   23 terms 
  Biochemical function     catalytic activity     16 terms  


    Added reference    
DOI no: 10.1073/pnas.022646999 Proc Natl Acad Sci U S A 99:1212-1217 (2002)
PubMed id: 11818540  
Crystal structure of the stimulatory complex of GTP cyclohydrolase I and its feedback regulatory protein GFRP.
N.Maita, K.Okada, K.Hatakeyama, T.Hakoshima.
In the presence of phenylalanine, GTP cyclohydrolase I feedback regulatory protein (GFRP) forms a stimulatory 360-kDa complex with GTP cyclohydrolase I (GTPCHI), which is the rate-limiting enzyme in the biosynthesis of tetrahydrobiopterin. The crystal structure of the stimulatory complex reveals that the GTPCHI decamer is sandwiched by two GFRP homopentamers. Each GFRP pentamer forms a symmetrical five-membered ring similar to beta-propeller. Five phenylalanine molecules are buried inside each interface between GFRP and GTPCHI, thus enhancing the binding of these proteins. The complex structure suggests that phenylalanine-induced GTPCHI x GFRP complex formation enhances GTPCHI activity by locking the enzyme in the active state.
  Selected figure(s)  
Figure 1.
Fig. 1. Reaction scheme and regulation mechanisms of the GTPCHI·GFRP complex. DOPA, 3,4-dihydroxyphenylalanine.
Figure 6.
Fig. 6. Superimposition of the GFRP monomers in the stimulatory (Stim, green) and free (red) forms. (Inset) A close-up view around Ile-10.
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
  20633294 F.Dabo, A.Grönbladh, F.Nyberg, I.Sundström-Poromaa, and H.Akerud (2010).
Different SNP combinations in the GCH1 gene and use of labor analgesia.
  Mol Pain, 6, 41.  
19101819 B.Chavan, W.Beazley, J.M.Wood, H.Rokos, H.Ichinose, and K.U.Schallreuter (2009).
H(2)O(2) increases de novo synthesis of (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin via GTP cyclohydrolase I and its feedback regulatory protein in vitiligo.
  J Inherit Metab Dis, 32, 86-94.  
19767425 B.Sankaran, S.A.Bonnett, K.Shah, S.Gabriel, R.Reddy, P.Schimmel, D.A.Rodionov, 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
19234759 N.Longo (2009).
Disorders of biopterin metabolism.
  J Inherit Metab Dis, 32, 333-342.  
16778797 B.Chavan, J.M.Gillbro, H.Rokos, and K.U.Schallreuter (2006).
GTP cyclohydrolase feedback regulatory protein controls cofactor 6-tetrahydrobiopterin synthesis in the cytosol and in the nucleus of epidermal keratinocytes and melanocytes.
  J Invest Dermatol, 126, 2481-2489.  
17057711 I.Tegeder, M.Costigan, R.S.Griffin, A.Abele, I.Belfer, H.Schmidt, C.Ehnert, J.Nejim, C.Marian, J.Scholz, T.Wu, A.Allchorne, L.Diatchenko, A.M.Binshtok, D.Goldman, J.Adolph, S.Sama, S.J.Atlas, W.A.Carlezon, A.Parsegian, J.Lötsch, R.B.Fillingim, W.Maixner, G.Geisslinger, M.B.Max, and C.J.Woolf (2006).
GTP cyclohydrolase and tetrahydrobiopterin regulate pain sensitivity and persistence.
  Nat Med, 12, 1269-1277.  
16696853 L.Swick, and G.Kapatos (2006).
A yeast 2-hybrid analysis of human GTP cyclohydrolase I protein interactions.
  J Neurochem, 97, 1447-1455.  
16010344 M.Fischer, and A.Bacher (2005).
Biosynthesis of flavocoenzymes.
  Nat Prod Rep, 22, 324-350.  
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.  
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.