PDBsum entry: 1g8m

Transferase, hydrolase

PDB id: 1g8m

Contents

Protein chains

590 a.a. *

Ligands

__G

Metals

__K ×2

Waters ×744

* Residue conservation analysis

PDB id:

1g8m

Name:

Transferase, hydrolase

Title:

Crystal structure of avian atic, a bifunctional transformylase and cyclohydrolase enzyme in purine biosynthesis at 1.75 ang. Resolution

Structure:

Aicar transformylase-imp cyclohydrolase. Chain: a, b. Fragment: aminoimidazole carboxamide ribonucleotide transformylase - inosine monophosphate cyclohydrolase. 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. Expression_system_taxid: 562.

Biol. unit:

Dimer (from PQS)

Resolution:

1.75Å R-factor: 0.200 R-free: 0.216

Authors:

S.E.Greasley,P.Horton,G.P.Beardsley,S.J.Benkovic,I.A.Wilson

Key ref:

S.E.Greasley et al. (2001). Crystal structure of a bifunctional transformylase and cyclohydrolase enzyme in purine biosynthesis. Nat Struct Biol, 8, 402-406. PubMed id: 11323713 DOI: 10.1038/87555

Date:

17-Nov-00 Release date: 27-Apr-01

Protein chains

P31335  (PUR9_CHICK) -  Bifunctional purine biosynthesis protein PURH

Seq: 593 a.a.

Struc: 591 a.a.

Enzyme reactions

• Enzyme class 2: E.C.2.1.2.3 - Phosphoribosylaminoimidazolecarboxamide formyltransferase.
• 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 = tetrahydrofolate + 5-formamido-1-(5-phospho-D- ribosyl)imidazole-4-carboxamide (Bound ligand (Het Group name = G) matches with 92.00% similarity)

• Enzyme class 3: E.C.3.5.4.10 - Imp cyclohydrolase.

Pathway:

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

IMP (Bound ligand (Het Group name = G) matches with 95.00% similarity) + 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 

• Cellular component: mitochondrion (1 term)
• Biological process: metabolic process (3 terms)
• Biochemical function: catalytic activity (6 terms)

reference

DOI no: 10.1038/87555

Nat Struct Biol 8:402-406 (2001)

PubMed id: 11323713

Crystal structure of a bifunctional transformylase and cyclohydrolase enzyme in purine biosynthesis.

S.E.Greasley, P.Horton, J.Ramcharan, G.P.Beardsley, S.J.Benkovic, I.A.Wilson.

ABSTRACT

ATIC, the product of the purH gene, is a 64 kDa bifunctional enzyme that possesses the final two activities in de novo purine biosynthesis, AICAR transformylase and IMP cyclohydrolase. The crystal structure of avian ATIC has been determined to 1.75 A resolution by the MAD method using a Se-methionine modified enzyme. ATIC forms an intertwined dimer with an extensive interface of approximately 5,000 A(2) per monomer. Each monomer is composed of two novel, separate functional domains. The N-terminal domain (up to residue 199) is responsible for the IMPCH activity, whereas the AICAR Tfase activity resides in the C-terminal domain (200-593). The active sites of the IMPCH and AICAR Tfase domains are approximately 50 A apart, with no structural evidence of a tunnel connecting the two active sites. The crystal structure of ATIC provides a framework to probe both catalytic mechanisms and to design specific inhibitors for use in cancer chemotherapy and inflammation.

Selected figure(s)

Figure 1.
Figure 1. Structure and function of ATIC. a, Reactions catalyzed by ATIC and the folate cofactor (10-f-THF). b, Stereo view of the crystal structure of the avATIC dimer. Monomer A is colored in blue arrows ( -strands) and green ribbons (helices) with yellow connecting residues, while monomer B is colored red ( -strands), orange (helices) and purple (connecting). The two purple spheres located near the C-termini represent bound potassium ions. Residue 199, the last residue in the IMPCH domain, is labeled along with the N- and C-termini. The bound GMP is shown in a ball-and-stick representation, and ^* indicates the approximate position of the phosphate of bound ligands in the IMPCH (bottom, black) and AICAR Tfase (top, black and blue) active sites, which are separated by 50 Å (black ^*).

Figure 3.
Figure 3. The AICAR Tfase domain. a, Stereo view of the structure of the AICAR Tfase domain colored by subdomains 2−4, as assessed by DOMID (Guogusng Lu, Lund University). The labeled residues correspond to the last residue of each domain. The position of the bound potassium ion is shown as a purple sphere (not shown is domain 1, the IMPCH domain). b, Superposition of the C trace of domain 2 (green) and domain 4 (yellow) showing internal duplication in the AICAR Tfase region. ^* indicates the location of domain 3 which was omitted for clarity. Conserved -strands are labeled 1−5, and -helices are labeled A−D. The equivalent main chain atoms of the core structures of domains 2 and 4 superimpose with r.m.s. deviations of 1.53 Å (monomer A) and 1.54 Å (monomer B). c, Cartoon of the topology (as in Fig. 2b) of domains 2 and 4. The regions that are structurally homologous have been labeled and colored as in (a,b).

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Biol (2001, 8, 402-406) copyright 2001.

Figures were selected by the author.