Publication Abstract from PubMed
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.
Crystal structure of a bifunctional transformylase and cyclohydrolase enzyme in purine biosynthesis.,Greasley SE, Horton P, Ramcharan J, Beardsley GP, Benkovic SJ, Wilson IA Nat Struct Biol. 2001 May;8(5):402-6. PMID:11323713[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
