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Transferase, hydrolase PDB-id
1m9n
Biological unit* = asymmetric unit, as shown
(*as deduced by PQS)
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Protein chains
590 a.a. *
Ligands
AMZ ×2
XMP ×2
Metal ions
__K ×2
Waters ×511

* Residue conservation analysis
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PDB id: 1m9n
Name: Transferase, hydrolase
Title: Crystal structure of the homodimeric bifunctional transformylase and cyclohydrolase enzyme avian atic in complex with aicar and xmp at 1.93 angstroms.

Structure:
Aicar transformylase-imp cyclohydrolase. Chain: a, b. Synonym: bifunctional purine biosynthesis protein purh [includes phosphoribosylaminoimidazolecarboxamide formyltransferase (aicar transformylase) and imp cyclohydrolase (inosinicase, imp synthetase, atic)]. Engineered: yes

Source:
Gallus gallus. Chicken. Organism_taxid: 9031. Gene: purh. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Biological unit:
Dimer (from PQS)

UniProt:
Chains A, B: P31335 (PUR9_CHICK)
Pfam   ArchSchema ?
Seq:
Struc:
Seq:
Struc:
Seq: 593 a.a.
Struc: 590 a.a.
Key:    PfamA domain
 Secondary structure  CATH domain

Enzyme class 1:
E.C.2.1.2.3   [IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

Reaction:
10-formyltetrahydrofolate + 5-amino-1-(5-phospho-D-ribosyl)imidazole-4- carboxamide = tetrahydrofolate + 5-formamido-1-(5-phospho-D- ribosyl)imidazole-4-carboxamide (see diagram below)

Pathway:
Purine Biosynthesis (late stages)

Enzyme class 2:
E.C.3.5.4.10   [IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

Reaction:
IMP + H2O = 5-formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide (see diagram below)

Pathway:
  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.

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

Related entries:
1g8m
crystal structure of avian atic, a bifunctional
transformylase and cyclohydrolase enzyme in purine
biosynthesis at 1.75 ang. Resolution
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Enzyme reaction for E.C.2.1.2.3 (Chains A, B)


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
Enzyme reaction for E.C.3.5.4.10 (Chains A, B)


IMP
+
H(2)O
=

5-formamido-1-(5-phospho-D-ribosyl)imidazole-4- carboxamide
Bound ligand (Het Group name = XMP)
corresponds exactly
Molecule diagrams generated from .mol files obtained from the KEGG ftp site.

 
    Key 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
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.