'''Crystal Structure Of Unliganded Form Of Mycobacterium tuberculosis Guanylate Kinase'''
===Crystal Structure Of Unliganded Form Of Mycobacterium tuberculosis Guanylate Kinase===
==Overview==
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Bacterial nucleoside monophosphate (NMP) kinases, which convert NMPs to nucleoside diphosphates (NDP), are investigated as potential antibacterial targets against pathogenic bacteria. Herein, we report the biochemical and structural characterization of GMP kinase from Mycobacterium tuberculosis (GMPKMt). GMPKMt is a monomer with an unusual specificity for ATP as a phosphate donor, a lower catalytic efficiency compared with eukaryotic GMPKs, and it carries two redox-sensitive cysteines in the central CORE domain. These properties were analyzed in the light of the high-resolution crystal structures of unbound, GMP-bound, and GDP-bound GMPKMt. The latter structure was obtained in both an oxidized form, in which the cysteines form a disulfide bridge, and a reduced form which is expected to correspond to the physiological enzyme. GMPKMt has a modular domain structure as most NMP kinases. However, it departs from eukaryotic GMPKs by the unusual conformation of its CORE domain, and by its partially open LID and GMP-binding domains which are the same in the apo-, GMP-bound, and GDP-bound forms. GMPKMt also features a unique GMP binding site which is less close-packed than that of mammalian GMPKs, and in which the replacement of a critical tyrosine by a serine removes a catalytic interaction. In contrast, the specificity of GMPKMt for ATP may be a general feature of GMPKs because of an invariant structural motif that recognizes the adenine base. Altogether, differences in domain dynamics and GMP binding between GMPKMt and mammalian GMPKs should reveal clues for the design of GMPKMt-specific inhibitors.
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==About this Structure==
==About this Structure==
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[[Category: Gmp kinase]]
[[Category: Gmp kinase]]
[[Category: Guanylate kinase]]
[[Category: Guanylate kinase]]
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Revision as of 15:58, 29 July 2008
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Crystal Structure Of Unliganded Form Of Mycobacterium tuberculosis Guanylate KinaseCrystal Structure Of Unliganded Form Of Mycobacterium tuberculosis Guanylate Kinase
Unique GMP-binding site in Mycobacterium tuberculosis guanosine monophosphate kinase., Hible G, Christova P, Renault L, Seclaman E, Thompson A, Girard E, Munier-Lehmann H, Cherfils J, Proteins. 2006 Feb 1;62(2):489-500. PMID:16288457
