PDBsum entry 1oz0

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protein ligands metals Protein-protein interface(s) links
Transferase, hydrolase PDB id
Protein chains
590 a.a. *
PO4 ×2
MS1 ×2
__K ×2
Waters ×378
* Residue conservation analysis
PDB id:
Name: Transferase, hydrolase
Title: Crystal structure of the homodimeric bifunctional transformylase and cyclohydrolase enzyme avian atic in complex with a multisubstrate adduct inhibitor beta-dadf.
Structure: Bifunctional purine biosynthesis protein purh. Chain: a, b. Synonym: aicar transformylase-imp cyclohydrolase, phosphoribosylaminoimidazolecarboxamide formyltransferase, inosinicase, imp synthetase, atic. Engineered: yes
Source: Gallus gallus. Chicken. Organism_taxid: 9031. Gene: atic or purh. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Biol. unit: Dimer (from PQS)
2.50Å     R-factor:   0.217     R-free:   0.269
Authors: D.W.Wolan,S.E.Greasley,M.J.Wall,S.J.Benkovic,I.A.Wilson
Key ref:
D.W.Wolan et al. (2003). Structure of avian AICAR transformylase with a multisubstrate adduct inhibitor beta-DADF identifies the folate binding site. Biochemistry, 42, 10904-10914. PubMed id: 12974624 DOI: 10.1021/bi030106h
07-Apr-03     Release date:   30-Sep-03    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P31335  (PUR9_CHICK) -  Bifunctional purine biosynthesis protein PURH
593 a.a.
590 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
Bound ligand (Het Group name = MS1)
matches with 56.00% similarity
+ 5-amino-1-(5-phospho-D-ribosyl)imidazole-4- carboxamide
= tetrahydrofolate
+ 5-formamido-1-(5-phospho-D- ribosyl)imidazole-4-carboxamide
   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
= 5-formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide
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     cytosol   1 term 
  Biological process     metabolic process   6 terms 
  Biochemical function     catalytic activity     6 terms  


DOI no: 10.1021/bi030106h Biochemistry 42:10904-10914 (2003)
PubMed id: 12974624  
Structure of avian AICAR transformylase with a multisubstrate adduct inhibitor beta-DADF identifies the folate binding site.
D.W.Wolan, S.E.Greasley, M.J.Wall, S.J.Benkovic, I.A.Wilson.
The penultimate catalytic step of the purine de novo synthesis pathway is the conversion of aminoimidazole-4-carboxamide ribonucleotide (AICAR) to 5-formyl-AICAR that requires the cofactor N(10)-formyl-tetrahydrofolate as the formyl donor. This reaction is catalyzed by the AICAR transformylase domain of the bifunctional enzyme AICAR transformylase/inosine monophosphate cyclohydrolase (ATIC). Identification of the location of the AICAR transformylase active site was previously elucidated from the crystal structure of the avian ATIC with bound substrate AICAR; however, due to the absence of any bound folate, the folate binding region of the active site could not be identified. Here, we have determined the homodimeric crystal structure of avian ATIC in complex with the ATIC-specific multisubstrate adduct inhibitor beta-DADF to 2.5 A resolution. Beta-DADF encompasses both the AICAR and folate moieties into a single covalently linked entity, thereby allowing for the characterization of the folate binding pocket of the AICAR transformylase active site. Beta-DADF is intimately bound at the dimer interface of the transformylase domains with the majority of AICAR moiety interactions occurring within one subunit, whereas the primary interactions to the folate occur with the opposing subunit. The crystal structure suggests that a buried Lys(267) is transiently protonated during formyl transfer allowing for the stabilization of the oxyanion transition state and subsequent protonation of N10 on the tetrahydrofolate leaving group. Furthermore, the beta-DADF-bound structure provides a more optimal three-dimensional scaffold to improve the design of specific antineoplastic agents.

Literature references that cite this PDB file's key reference

  PubMed id Reference
18712276 Y.Zhang, M.Morar, and S.E.Ealick (2008).
Structural biology of the purine biosynthetic pathway.
  Cell Mol Life Sci, 65, 3699-3724.  
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
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
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