1jvn
From Proteopedia
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CRYSTAL STRUCTURE OF IMIDAZOLE GLYCEROL PHOSPHATE SYNTHASE: A TUNNEL THROUGH A (BETA/ALPHA)8 BARREL JOINS TWO ACTIVE SITES
Overview
BACKGROUND: Imidazole glycerol phosphate synthase catalyzes a two-step, reaction of histidine biosynthesis at the bifurcation point with the, purine de novo pathway. The enzyme is a new example of intermediate, channeling by glutamine amidotransferases in which ammonia generated by, hydrolysis of glutamine is channeled to a second active site where it acts, as a nucleophile. In this case, ammonia reacts in a cyclase domain to, produce imidazole glycerol phosphate and an intermediate of purine, biosynthesis. The enzyme is also a potential target for drug and herbicide, development since the histidine pathway does not occur in mammals., RESULTS: The 2.1 A crystal structure of imidazole glycerol phosphate, synthase from yeast reveals extensive interaction of the glutaminase and, cyclase catalytic domains. At the domain interface, the glutaminase active, site points into the bottom of the (beta/alpha)(8) barrel of the cyclase, domain. An ammonia tunnel through the (beta/alpha)(8) barrel connects the, glutaminase docking site at the bottom to the cyclase active site at the, top. A conserved "gate" of four charged residues controls access to the, tunnel. CONCLUSIONS: This is the first structure in which all the, components of the ubiquitous (beta/alpha)(8) barrel fold, top, bottom, and, interior, take part in enzymatic function. Intimate contacts between the, barrel domain and the glutaminase active site appear to be poised for, crosstalk between catalytic centers in response to substrate binding at, the cyclase active site. The structure provides a number of potential, sites for inhibitor development in the active sites and in a conserved, interdomain cavity.
About this Structure
1JVN is a Single protein structure of sequence from Saccharomyces cerevisiae with NI, SO4 and POP as ligands. Full crystallographic information is available from OCA.
Reference
Crystal structure of imidazole glycerol phosphate synthase: a tunnel through a (beta/alpha)8 barrel joins two active sites., Chaudhuri BN, Lange SC, Myers RS, Chittur SV, Davisson VJ, Smith JL, Structure. 2001 Oct;9(10):987-97. PMID:11591353
Page seeded by OCA on Tue Nov 20 18:36:48 2007
