1ox4
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TOWARDS UNDERSTANDING THE MECHANISM OF THE COMPLEX CYCLIZATION REACTION CATALYZED BY IMIDAZOLE GLYCEROPHOSPHATE SYNTHASE
OverviewOverview
Imidazole glycerol phosphate synthase catalyzes formation of the imidazole, ring in histidine biosynthesis. The enzyme is also a glutamine, amidotransferase, which produces ammonia in a glutaminase active site and, channels it through a 30-A internal tunnel to a cyclase active site., Glutaminase activity is impaired in the resting enzyme, and stimulated by, substrate binding in the cyclase active site. The signaling mechanism was, investigated in the crystal structure of a ternary complex in which the, glutaminase active site was inactivated by a glutamine analogue and the, unstable cyclase substrate was cryo-trapped in the active site. The, orientation of, N(1)-(5'-phosphoribulosyl)-formimino-5-aminoimidazole-4-carboxamide, ribonucleotide in the cyclase active site implicates one side of the, cyclase domain in signaling to the glutaminase domain. This side of the, cyclase domain contains the interdomain hinge. Two interdomain hydrogen, bonds, which do not exist in more open forms of the enzyme, are proposed, as molecular signals. One hydrogen bond connects the cyclase domain to the, substrate analogue in the glutaminase active site. The second hydrogen, bond connects to a peptide that forms an oxyanion hole for stabilization, of transient negative charge during glutamine hydrolysis. Peptide, rearrangement induced by a fully closed domain interface is proposed to, activate the glutaminase by unblocking the oxyanion hole. This, interpretation is consistent with biochemical results [Myers, R. S., et, al., (2003) Biochemistry 42, 7013-7022, the accompanying paper in this, issue] and with structures of the free enzyme and a binary complex with a, second glutamine analogue.
About this StructureAbout this Structure
1OX4 is a Protein complex structure of sequences from Saccharomyces cerevisiae with SO4, NI and POP as ligands. Full crystallographic information is available from OCA.
ReferenceReference
Toward understanding the mechanism of the complex cyclization reaction catalyzed by imidazole glycerolphosphate synthase: crystal structures of a ternary complex and the free enzyme., Chaudhuri BN, Lange SC, Myers RS, Davisson VJ, Smith JL, Biochemistry. 2003 Jun 17;42(23):7003-12. PMID:12795595
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