1znx

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spinqualitylabelsall models 1znx, resolution 2.35Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Crystal Structure Of Mycobacterium tuberculosis Guanylate Kinase In Complex With GMP

Overview

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.

About this Structure

1ZNX is a Single protein structure of sequence from Mycobacterium tuberculosis with 5GP as ligand. Active as Guanylate kinase, with EC number 2.7.4.8 Full crystallographic information is available from OCA.

Reference

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

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