Toward Understanding the Mechanism of the Complex Cyclization Reaction Catalyzed by Imidazole Glycerolphosphate Synthase: Crystal Structures of a Ternary Complex and the Free Enzyme,

• DOI: 10.1021/bi034320h
• Publication Date: 2003-06-10T04:48:32Z
• Authors: Barnali N. Chaudhuri; Stephanie C. Lange; Rebecca S. Myers; V. Jo Davisson; Janet L. Smith
• Keywords: Ternary complex; Imidazole

Imidazole glycerol phosphate synthase catalyzes formation of the imidazole ring in histidine biosynthesis. The enzyme is also a glutamine amidotransferase, which produces ammonia glutaminase active site and channels it through 30-Å internal tunnel to cyclase site. Glutaminase activity impaired resting enzyme, stimulated by substrate binding signaling mechanism was investigated crystal structure ternary complex inactivated analogue unstable cryo-trapped orientation N1-(5'-phosphoribulosyl)-formimino-5-aminoimidazole-4-carboxamide ribonucleotide implicates one side domain domain. This contains interdomain hinge. Two hydrogen bonds, do not exist more open forms are proposed as molecular signals. One bond connects second peptide that an oxyanion hole for stabilization transient negative charge during hydrolysis. Peptide rearrangement induced fully closed interface activate unblocking hole. interpretation consistent with biochemical results [Myers, R. S., et al., (2003) Biochemistry 42, 7013−7022, accompanying paper this issue] structures free binary analogue.