1G8M

CRYSTAL STRUCTURE OF AVIAN ATIC, A BIFUNCTIONAL TRANSFORMYLASE AND CYCLOHYDROLASE ENZYME IN PURINE BIOSYNTHESIS AT 1.75 ANG. RESOLUTION

Summary for 1G8M

• Entry DOI: 10.2210/pdb1g8m/pdb
• Descriptor: AICAR TRANSFORMYLASE-IMP CYCLOHYDROLASE, POTASSIUM ION, GUANOSINE-5'-MONOPHOSPHATE, ... (4 entities in total)
• Functional Keywords: homodimer, 2 functional domains; impch domain = alpha/beta/alpha; aicar tfase = 2 alpha/beta/alpha domains, 1 alpha + beta domain, transferase, hydrolase
• Biological source: Gallus gallus (chicken)
• Total number of polymer chains: 2
• Total formula weight: 130374.73

Authors

Greasley, S.E.,Horton, P.,Beardsley, G.P.,Benkovic, S.J.,Wilson, I.A. (deposition date: 2000-11-17, release date: 2001-04-27, Last modification date: 2024-10-16)

Primary citation

Greasley, S.E.,Horton, P.,Ramcharan, J.,Beardsley, G.P.,Benkovic, S.J.,Wilson, I.A.
Crystal structure of a bifunctional transformylase and cyclohydrolase enzyme in purine biosynthesis.
Nat.Struct.Biol., 8:402-406, 2001

PubMed 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.

PubMed: 11323713
DOI: 10.1038/87555

Experimental method

X-RAY DIFFRACTION (1.75 Å)