PDBsum entry 1pkx

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protein ligands metals Protein-protein interface(s) links
Transferase, hydrolase PDB id
Protein chain
588 a.a. *
XMP ×2
__K ×4
Waters ×977
* Residue conservation analysis
PDB id:
Name: Transferase, hydrolase
Title: Crystal structure of human atic in complex with xmp
Structure: Bifunctional purine biosynthesis protein purh. Chain: a, b, c, d. Synonym: atic. Engineered: yes. Other_details: includes: phosphoribosylaminoimidazolecarboxamide formyltransferase (aicar transformylase) and imp cyclohydrolase (inosinicase) (imp synthetase)
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: atic. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Dimer (from PQS)
1.90Å     R-factor:   0.211     R-free:   0.249
Authors: D.W.Wolan,C.G.Cheong,S.E.Greasley,I.A.Wilson
Key ref:
D.W.Wolan et al. (2004). Structural insights into the human and avian IMP cyclohydrolase mechanism via crystal structures with the bound XMP inhibitor. Biochemistry, 43, 1171-1183. PubMed id: 14756553 DOI: 10.1021/bi030162i
06-Jun-03     Release date:   17-Feb-04    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P31939  (PUR9_HUMAN) -  Bifunctional purine biosynthesis protein PURH
592 a.a.
588 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class 2: E.C.  - Phosphoribosylaminoimidazolecarboxamide formyltransferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

Purine Biosynthesis (late stages)
      Reaction: 10-formyltetrahydrofolate + 5-amino-1-(5-phospho-D-ribosyl)imidazole-4- carboxamide = tetrahydrofolate + 5-formamido-1-(5-phospho-D- ribosyl)imidazole-4-carboxamide
+ 5-amino-1-(5-phospho-D-ribosyl)imidazole-4- carboxamide
= tetrahydrofolate
5-formamido-1-(5-phospho-D- ribosyl)imidazole-4-carboxamide
Bound ligand (Het Group name = XMP)
corresponds exactly
   Enzyme class 3: E.C.  - Imp cyclohydrolase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

      Reaction: IMP + H2O = 5-formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide
+ H(2)O
Bound ligand (Het Group name = XMP)
corresponds exactly
Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   4 terms 
  Biological process     brainstem development   17 terms 
  Biochemical function     catalytic activity     6 terms  


DOI no: 10.1021/bi030162i Biochemistry 43:1171-1183 (2004)
PubMed id: 14756553  
Structural insights into the human and avian IMP cyclohydrolase mechanism via crystal structures with the bound XMP inhibitor.
D.W.Wolan, C.G.Cheong, S.E.Greasley, I.A.Wilson.
Within de novo purine biosynthesis, the AICAR transformylase and IMP cyclohydrolase activities of the bifunctional enzyme ATIC convert the intermediate AICAR to the final product of the pathway, IMP. Identification of the AICAR transformylase active site and a proposed formyl transfer mechanism have already resulted from analysis of crystal structures of avian ATIC in complex with substrate and/or inhibitors. Herein, we focus on the IMPCH active site and the cyclohydrolase mechanism through comparison of crystal structures of XMP inhibitor complexes of human ATIC at 1.9 A resolution with the previously determined avian enzyme. This first human ATIC structure was also determined to ascertain whether any subtle structural differences, compared to the homologous avian enzyme, should be taken into account for structure-based inhibitor design. These structural comparisons, as well as comparative analyses with other IMP and XMP binding proteins, have enabled a catalytic mechanism to be formulated. The primary role of the IMPCH active site appears to be to induce a reconfiguration of the substrate FAICAR to a less energetically favorable, but more reactive, conformer. Backbone (Arg64 and Lys66) and side chain interactions (Thr67) in the IMPCH active site reorient the 4-carboxamide from the preferred conformer that binds to the AICAR Tfase active site to one that promotes intramolecular cyclization. Other backbone amides (Ile126 and Gly127) create an oxyanion hole that helps orient the formyl group for nucleophilic attack by the 4-carboxamide amine and then stabilize the anionic intermediate. Several other residues, including Lys66, Tyr104, Asp125, and Lys137', provide substrate specificity and likely enhance the catalytic rate through contributions to acid-base catalysis.

Literature references that cite this PDB file's key reference

  PubMed id Reference
18723842 J.Zhang, R.Sprung, J.Pei, X.Tan, S.Kim, H.Zhu, C.F.Liu, N.V.Grishin, and Y.Zhao (2009).
Lysine acetylation is a highly abundant and evolutionarily conserved modification in Escherichia coli.
  Mol Cell Proteomics, 8, 215-225.  
18260100 H.L.Axelrod, D.McMullan, S.S.Krishna, M.D.Miller, M.A.Elsliger, P.Abdubek, E.Ambing, T.Astakhova, D.Carlton, H.J.Chiu, T.Clayton, L.Duan, J.Feuerhelm, S.K.Grzechnik, J.Hale, G.W.Han, J.Haugen, L.Jaroszewski, K.K.Jin, H.E.Klock, M.W.Knuth, E.Koesema, A.T.Morse, E.Nigoghossian, L.Okach, S.Oommachen, J.Paulsen, K.Quijano, R.Reyes, C.L.Rife, H.van den Bedem, D.Weekes, A.White, G.Wolf, Q.Xu, K.O.Hodgson, J.Wooley, A.M.Deacon, A.Godzik, S.A.Lesley, and I.A.Wilson (2008).
Crystal structure of AICAR transformylase IMP cyclohydrolase (TM1249) from Thermotoga maritima at 1.88 A resolution.
  Proteins, 71, 1042-1049.
PDB code: 1zcz
18712276 Y.Zhang, M.Morar, and S.E.Ealick (2008).
Structural biology of the purine biosynthetic pathway.
  Cell Mol Life Sci, 65, 3699-3724.  
18069798 Y.Zhang, R.H.White, and S.E.Ealick (2008).
Crystal structure and function of 5-formaminoimidazole-4-carboxamide ribonucleotide synthetase from Methanocaldococcus jannaschii.
  Biochemistry, 47, 205-217.
PDB codes: 2r7k 2r7l 2r7m 2r7n 2r84 2r85 2r86 2r87
17324932 L.Xu, Y.Chong, I.Hwang, A.D'Onofrio, K.Amore, G.P.Beardsley, C.Li, A.J.Olson, D.L.Boger, and I.A.Wilson (2007).
Structure-based design, synthesis, evaluation, and crystal structures of transition state analogue inhibitors of inosine monophosphate cyclohydrolase.
  J Biol Chem, 282, 13033-13046.
PDB codes: 2b0w 2b1g 2b1i 2iu0 2iu3
17407260 Y.N.Kang, A.Tran, R.H.White, and S.E.Ealick (2007).
A novel function for the N-terminal nucleophile hydrolase fold demonstrated by the structure of an archaeal inosine monophosphate cyclohydrolase.
  Biochemistry, 46, 5050-5062.
PDB codes: 2ntk 2ntl 2ntm
14966129 C.G.Cheong, D.W.Wolan, S.E.Greasley, P.A.Horton, G.P.Beardsley, and I.A.Wilson (2004).
Crystal structures of human bifunctional enzyme aminoimidazole-4-carboxamide ribonucleotide transformylase/IMP cyclohydrolase in complex with potent sulfonyl-containing antifolates.
  J Biol Chem, 279, 18034-18045.
PDB codes: 1p4r 1pl0
15355974 L.Xu, C.Li, A.J.Olson, and I.A.Wilson (2004).
Crystal structure of avian aminoimidazole-4-carboxamide ribonucleotide transformylase in complex with a novel non-folate inhibitor identified by virtual ligand screening.
  J Biol Chem, 279, 50555-50565.
PDB code: 1thz
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 code is shown on the right.