1n5k: Difference between revisions

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 <StructureSection load='1n5k' size='340' side='right'caption='[[1n5k]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1n5k]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/"bacillus_tuberculosis"_(zopf_1883)_klein_1884 "bacillus tuberculosis" (zopf 1883) klein 1884]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1N5K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1N5K FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1n5k]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1N5K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1N5K FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=TMP:THYMIDINE-5-PHOSPHATE'>TMP</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1gsi|1gsi]], [[1g3u|1g3u]], [[1n5i|1n5i]], [[1n5j|1n5j]], [[1n5l|1n5l]]</div></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=TMP:THYMIDINE-5-PHOSPHATE'>TMP</scene></td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/dTMP_kinase dTMP kinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.4.9 2.7.4.9] </span></td></tr>
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1n5k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1n5k OCA], [https://pdbe.org/1n5k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1n5k RCSB], [https://www.ebi.ac.uk/pdbsum/1n5k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1n5k ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[https://www.uniprot.org/uniprot/KTHY_MYCTU KTHY_MYCTU]] Catalyzes the reversible phosphorylation of deoxythymidine monophosphate (dTMP) to deoxythymidine diphosphate (dTDP), using ATP as its preferred phosphoryl donor. Situated at the junction of both de novo and salvage pathways of deoxythymidine triphosphate (dTTP) synthesis, is essential for DNA synthesis and cellular growth. Has a broad specificity for nucleoside triphosphates, being highly active with ATP or dATP as phosphate donors, and less active with ITP, GTP, CTP and UTP.[HAMAP-Rule:MF_00165]
+[https://www.uniprot.org/uniprot/KTHY_MYCTU KTHY_MYCTU] Catalyzes the reversible phosphorylation of deoxythymidine monophosphate (dTMP) to deoxythymidine diphosphate (dTDP), using ATP as its preferred phosphoryl donor. Situated at the junction of both de novo and salvage pathways of deoxythymidine triphosphate (dTTP) synthesis, is essential for DNA synthesis and cellular growth. Has a broad specificity for nucleoside triphosphates, being highly active with ATP or dATP as phosphate donors, and less active with ITP, GTP, CTP and UTP.[HAMAP-Rule:MF_00165]
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
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 </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1n5k ConSurf].
 <div style="clear:both"></div>
-<div style="background-color:#fffaf0;">
-== Publication Abstract from PubMed ==
-Mycobacterium tuberculosis TMP kinase (TMPK(Mtub)) represents a promising target for developing drugs against tuberculosis because the configuration of its active site is unique in the TMPK family. To help elucidate the phosphorylation mechanism employed by this enzyme, structural changes occurring upon binding of substrates and subsequent catalysis were investigated by protein crystallography. Six new structures of TMPK(Mtub) were solved at a resolution better than 2.3A, including the first structure of an apo-TMPK, obtained by triggering catalysis in a crystal of a TMPK(Mtub)-TMP complex, which resulted in the release of the TDP product. A series of snapshots along the reaction pathway is obtained, revealing the closure of the active site in going from an empty to a fully occupied state, suggestive of an induced-fit mechanism typical of NMPKs. However, in TMPK(Mtub) the LID closure couples to the binding with an unusual location for a magnesium ion coordinating TMP in the active site. Our data suggest strongly that this ion is required for catalysis, acting as a clamp, possibly in concert with Arg95, to neutralise electrostatic repulsion between the anionic substrates, optimise their proper alignment and activate them through direct and water-mediated interactions. The 3'-hydroxyl moiety of TMP, critical to metal stabilisation, appears to be a target of choice for the design of potent inhibitors. On the other hand, the usual NTP-bound magnesium is not seen in our structures and Arg14, a P-loop residue unique to TMPK(Mtub), may take over its role. Therefore, TMPK(Mtub) seems to have swapped the use of a metal ion as compared with e.g. human TMPK. Finally, TTP was observed in crystals of TMPK(Mtub), locked by Arg14, thus providing a structural explanation for the observed inhibitory effect of TTP putatively involved in a mechanism of feedback regulation of the enzymatic activity.
-Mycobacterium tuberculosis thymidylate kinase: structural studies of intermediates along the reaction pathway.,Fioravanti E, Haouz A, Ursby T, Munier-Lehmann H, Delarue M, Bourgeois D J Mol Biol. 2003 Apr 11;327(5):1077-92. PMID:12662932<ref>PMID:12662932</ref>
-From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-</div>
-<div class="pdbe-citations 1n5k" style="background-color:#fffaf0;"></div>
 ==See Also==
 *[[Thymidylate kinase 3D structures|Thymidylate kinase 3D structures]]
-== References ==
-<references/>
 __TOC__
 </StructureSection>
 [[Category: Large Structures]]
-[[Category: DTMP kinase]]
+[[Category: Mycobacterium tuberculosis]]
-[[Category: Bourgeois, D]]
+[[Category: Bourgeois D]]
-[[Category: Delarue, M]]
+[[Category: Delarue M]]
-[[Category: Fioravanti, E]]
+[[Category: Fioravanti E]]
-[[Category: Haouz, A]]
+[[Category: Haouz A]]
-[[Category: Munier-Lehmann, H]]
+[[Category: Munier-Lehmann H]]
-[[Category: Ursby, T]]
+[[Category: Ursby T]]
-[[Category: Kinase]]
-[[Category: Transferase]]