1g3u: Difference between revisions
New page: left|200px<br /><applet load="1g3u" size="450" color="white" frame="true" align="right" spinBox="true" caption="1g3u, resolution 1.95Å" /> '''CRYSTAL STRUCTURE OF... |
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[[Image:1g3u.jpg|left|200px]]<br /><applet load="1g3u" size=" | [[Image:1g3u.jpg|left|200px]]<br /><applet load="1g3u" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="1g3u, resolution 1.95Å" /> | caption="1g3u, resolution 1.95Å" /> | ||
'''CRYSTAL STRUCTURE OF MYCOBACTERIUM TUBERCULOSIS THYMIDYLATE KINASE COMPLEXED WITH THYMIDINE MONOPHOSPHATE (TMP)'''<br /> | '''CRYSTAL STRUCTURE OF MYCOBACTERIUM TUBERCULOSIS THYMIDYLATE KINASE COMPLEXED WITH THYMIDINE MONOPHOSPHATE (TMP)'''<br /> | ||
==Overview== | ==Overview== | ||
The X-ray structure of Mycobacterium tuberculosis TMP kinase at 1.95 A | 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. | ||
==About this Structure== | ==About this Structure== | ||
1G3U is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis] with SO4, MG and TMP as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/dTMP_kinase dTMP kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.4.9 2.7.4.9] Full crystallographic information is available from [http:// | 1G3U is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis] with <scene name='pdbligand=SO4:'>SO4</scene>, <scene name='pdbligand=MG:'>MG</scene> and <scene name='pdbligand=TMP:'>TMP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/dTMP_kinase dTMP kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.4.9 2.7.4.9] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1G3U OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Barzu, O.]] | [[Category: Barzu, O.]] | ||
[[Category: Delarue, M.]] | [[Category: Delarue, M.]] | ||
[[Category: Gilles, A | [[Category: Gilles, A M.]] | ||
[[Category: Munier-Lehmann, H.]] | [[Category: Munier-Lehmann, H.]] | ||
[[Category: Sierra, I | [[Category: Sierra, I Li de la.]] | ||
[[Category: MG]] | [[Category: MG]] | ||
[[Category: SO4]] | [[Category: SO4]] | ||
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[[Category: transferase (atp:tmp phosphotransferase)]] | [[Category: transferase (atp:tmp phosphotransferase)]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:45:46 2008'' | ||
Revision as of 13:45, 21 February 2008
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CRYSTAL STRUCTURE OF MYCOBACTERIUM TUBERCULOSIS THYMIDYLATE KINASE COMPLEXED WITH THYMIDINE MONOPHOSPHATE (TMP)
OverviewOverview
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.
About this StructureAbout this Structure
1G3U is a Single protein structure of sequence from Mycobacterium tuberculosis with , and as ligands. Active as dTMP kinase, with EC number 2.7.4.9 Full crystallographic information is available from OCA.
ReferenceReference
X-ray structure of TMP kinase from Mycobacterium tuberculosis complexed with TMP at 1.95 A resolution., Li de la Sierra I, Munier-Lehmann H, Gilles AM, Barzu O, Delarue M, J Mol Biol. 2001 Aug 3;311(1):87-100. PMID:11469859
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