Kinetic Model of Imidazologlycerol-Phosphate Synthetase from Escherichia coli

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O. V. Demin^1*, I. I. Goryanin², S. Dronov², and G. V. Lebedeva¹

¹Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992 Moscow, Russia; fax: (7-095) 939-3181; E-mail: demin@genebee.msu.su

²GlaxoSmithKline, Gunnels Wood Road, Stevenage SG1 2NY, UK; E-mail: iig2468@gsk.com

^* To whom correspondence should be addressed.

Received March 18, 2004; Revision received June 4, 2004

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Based on the available experimental data, we developed a kinetic model of the catalytic cycle of imidazologlycerol-phosphate synthetase from Escherichia coli accounting for the synthetase and glutaminase activities of the enzyme. The rate equations describing synthetase and glutaminase activities of imidazologlycerol-phosphate synthetase were derived from this catalytic cycle. Using the literature data, we evaluated all kinetic parameters of the rate equations characterizing individually synthetase and glutaminase activities as well as the contribution of each activity depending on concentration of the substrates, products, and effectors. As shown, in the presence of 5´-phosphoribosylformimino-5-aminoimidazolo-4-carboxamideribonucleotide (ProFAR) and imidazologlycerol phosphate (IGP) glutaminase activity dominates over synthetase activity at sufficiently low concentrations of 5´-phosphoribulosylformimino-5-aminoimidazolo-4-carboxamideribonucleotide (PRFAR). Increased PRFAR concentrations resulted in decreased contribution of glutaminase activity and, consequently, increased the contribution of synthetase activity in the enzyme functioning.

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KEY WORDS: imidazologlycerol-phosphate synthetase, catalytic cycle, model

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