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

Nature Structural Biology
S E GreasleyIan 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.

Citations

Aug 21, 2008·Cellular and Molecular Life Sciences : CMLS·Y ZhangS E Ealick
Dec 29, 2012·Journal of the American Chemical Society·Eunhwa KoKevin Burgess
Apr 12, 2013·Chemical Communications : Chem Comm·Hong ZhaoStephen J Benkovic
Oct 1, 2011·The Journal of Biological Chemistry·Jérôme Le NoursEdward N Baker
Oct 11, 2013·Journal of Biochemistry·Gen-ichi SampeiGota Kawai
Dec 6, 2011·Acta Crystallographica. Section F, Structural Biology and Crystallization Communications·Xiaoting QiuYongxiang Gao
Feb 15, 2002·Journal of Bacteriology·Marion GraupnerRobert H White
Dec 3, 2005·Journal of Bacteriology·Rebecca F KinsingerRay Fall
Dec 8, 2010·Genetics·Jannell V Bazurto, Diana M Downs
Nov 21, 2015·Biophysical Journal·Bradley W DavisChristine D Keating
Jan 17, 2007·Journal of Molecular Biology·Shu-Xing LiRu-Chang Bi
May 19, 2018·The FEBS Journal·Marcella CamiciMaria Grazia Tozzi
Jul 6, 2012·Chembiochem : a European Journal of Chemical Biology·Ian B SpurrAli Tavassoli
Dec 22, 2007·Annals of the New York Academy of Sciences·Laura L Grochowski, Robert H White
Apr 15, 2005·Angewandte Chemie·Ali Tavassoli, Stephen J Benkovic
Oct 4, 2006·Physiological Reviews·Michael J Page, Enrico Di Cera
Nov 4, 2005·The Journal of Biological Chemistry·Enrico Di Cera
Nov 5, 2020·Critical Reviews in Food Science and Nutrition·Zengwen HuangGuosheng Xin
Nov 13, 2020·Critical Reviews in Biochemistry and Molecular Biology·Vidhi PareekStephen J Benkovic
Sep 10, 2004·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Shigeki ShichijoKyogo Itoh
Mar 15, 2003·The Journal of Biological Chemistry·Tzu-Ping KoShwu-Huey Liaw
Nov 24, 2004·Proteins·Yuan Qi, Nick V Grishin
May 25, 2005·Bioorganic & Medicinal Chemistry Letters·Kevin J CappsDale L Boger

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