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X-ray structure of TMP kinase from Mycobacterium tuberculosis complexed with TMP at 1.95 A resolution.

Abstract : The X-ray structure of Mycobacterium tuberculosis TMP kinase at 1.95 A resolution is described as a binary complex with its natural substrate TMP. Its main features involve: (i) a clear magnesium-binding site; (ii) an alpha-helical conformation for the so-called LID region; and (iii) a high density of positive charges in the active site. There is a network of interactions involving highly conserved side-chains of the protein, the magnesium ion, a sulphate ion mimicking the beta phosphate group of ATP and the TMP molecule itself. All these interactions conspire in stabilizing what appears to be the closed form of the enzyme. A complete multialignment of all (32) known sequences of TMP kinases is presented. Subtle differences in the TMP binding site were noted, as compared to the Escherichia coli, yeast and human enzyme structures, which have been reported recently. These differences could be used to design specific inhibitors of this essential enzyme of nucleotide metabolism. Two cases of compensatory mutations were detected in the TMP binding site of eukaryotic and prokaryotic enzymes. In addition, an intriguing high value of the electric field is reported in the vicinity of the phosphate group of TMP and the putative binding site of the gamma phosphate group of ATP.
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https://hal-pasteur.archives-ouvertes.fr/pasteur-00167054
Contributor : Hélène Munier-Lehmann <>
Submitted on : Tuesday, August 14, 2007 - 2:07:31 PM
Last modification on : Monday, January 13, 2020 - 5:08:10 PM

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Inès Li de la Sierra, Hélène Munier-Lehmann, Anne-Marie Gilles, Octavian Bârzu, Marc Delarue. X-ray structure of TMP kinase from Mycobacterium tuberculosis complexed with TMP at 1.95 A resolution.. Journal of Molecular Biology, Elsevier, 2001, 311 (1), pp.87-100. ⟨10.1006/jmbi.2001.4843⟩. ⟨pasteur-00167054⟩

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