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PDBsum entry 1m9n

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protein ligands metals Protein-protein interface(s) links
Transferase, hydrolase PDB id
1m9n
Jmol
Contents
Protein chains
590 a.a. *
Ligands
AMZ ×2
XMP ×2
Metals
__K ×2
Waters ×511
* Residue conservation analysis
PDB id:
1m9n
Name: Transferase, hydrolase
Title: Crystal structure of the homodimeric bifunctional transformy cyclohydrolase enzyme avian atic in complex with aicar and 1.93 angstroms.
Structure: Aicar transformylase-imp cyclohydrolase. Chain: a, b. Synonym: bifunctional purine biosynthesis protein purh [inc phosphoribosylaminoimidazolecarboxamide formyltransferase ( transformylase) and imp cyclohydrolase (inosinicase, imp sy atic)]. Engineered: yes
Source: Gallus gallus. Chicken. Organism_taxid: 9031. Gene: purh. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Biol. unit: Dimer (from PQS)
Resolution:
1.93Å     R-factor:   0.210     R-free:   0.244
Authors: D.W.Wolan,S.E.Greasly,G.P.Beardsley,I.A.Wilson
Key ref:
D.W.Wolan et al. (2002). Structural insights into the avian AICAR transformylase mechanism. Biochemistry, 41, 15505-15513. PubMed id: 12501179 DOI: 10.1021/bi020505x
Date:
29-Jul-02     Release date:   07-Jan-03    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P31335  (PUR9_CHICK) -  Bifunctional purine biosynthesis protein PURH
Seq:
Struc:
 
Seq:
Struc:
593 a.a.
590 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class 2: E.C.2.1.2.3  - Phosphoribosylaminoimidazolecarboxamide formyltransferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

      Pathway:
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
10-formyltetrahydrofolate
+
5-amino-1-(5-phospho-D-ribosyl)imidazole-4- carboxamide
Bound ligand (Het Group name = AMZ)
corresponds exactly
= tetrahydrofolate
+
5-formamido-1-(5-phospho-D- ribosyl)imidazole-4-carboxamide
Bound ligand (Het Group name = XMP)
corresponds exactly
   Enzyme class 3: E.C.3.5.4.10  - Imp cyclohydrolase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

      Pathway:
      Reaction: IMP + H2O = 5-formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide
IMP
+ H(2)O
=
5-formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide
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     cytosol   1 term 
  Biological process     metabolic process   6 terms 
  Biochemical function     catalytic activity     6 terms  

 

 
    reference    
 
 
DOI no: 10.1021/bi020505x Biochemistry 41:15505-15513 (2002)
PubMed id: 12501179  
 
 
Structural insights into the avian AICAR transformylase mechanism.
D.W.Wolan, S.E.Greasley, G.P.Beardsley, I.A.Wilson.
 
  ABSTRACT  
 
ATIC encompasses both AICAR transformylase and IMP cyclohydrolase activities that are responsible for the catalysis of the penultimate and final steps of the purine de novo synthesis pathway. The formyl transfer reaction catalyzed by the AICAR Tfase domain is substantially more demanding than that catalyzed by the other folate-dependent enzyme of the purine biosynthesis pathway, GAR transformylase. Identification of the AICAR Tfase active site and key catalytic residues is essential to elucidate how the non-nucleophilic AICAR amino group is activated for formyl transfer. Hence, the crystal structure of dimeric avian ATIC was determined as a complex with the AICAR Tfase substrate AICAR, as well as with an IMP cyclohydrolase inhibitor, XMP, to 1.93 A resolution. AICAR is bound at the dimer interface of the transformylase domains and forms an extensive hydrogen bonding network with a multitude of active site residues. The crystal structure suggests that the conformation of the 4-carboxamide of AICAR is poised to increase the nucleophilicity of the C5 amine, while proton abstraction occurs via His(268) concomitant with formyl transfer. Lys(267) is likely to be involved in the stabilization of the anionic formyl transfer transition state and in subsequent protonation of the THF leaving group.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
19068483 W.Wang, A.Fridman, W.Blackledge, S.Connelly, I.A.Wilson, R.B.Pilz, and G.R.Boss (2009).
The phosphatidylinositol 3-kinase/akt cassette regulates purine nucleotide synthesis.
  J Biol Chem, 284, 3521-3528.  
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
16308316 S.C.Chen, Y.C.Chang, C.H.Lin, C.H.Lin, and S.H.Liaw (2006).
Crystal structure of a bifunctional deaminase and reductase from Bacillus subtilis involved in riboflavin biosynthesis.
  J Biol Chem, 281, 7605-7613.  
15558583 Y.Qi, and N.V.Grishin (2005).
Structural classification of thioredoxin-like fold proteins.
  Proteins, 58, 376-388.  
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
15180998 S.H.Liaw, Y.J.Chang, C.T.Lai, H.C.Chang, and G.G.Chang (2004).
Crystal structure of Bacillus subtilis guanine deaminase: the first domain-swapped structure in the cytidine deaminase superfamily.
  J Biol Chem, 279, 35479-35485.
PDB code: 1wkq
12637534 T.P.Ko, J.J.Lin, C.Y.Hu, Y.H.Hsu, A.H.Wang, and S.H.Liaw (2003).
Crystal structure of yeast cytosine deaminase. Insights into enzyme mechanism and evolution.
  J Biol Chem, 278, 19111-19117.
PDB code: 1uaq
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.