1n5l: Difference between revisions

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-[[Image:1n5l.jpg|left|200px]]
-<!--
+==CRYSTAL STRUCTURE OF MYCOBACTERIUM TUBERCULOSIS THYMIDYLATE KINASE CRYSTALLIZED IN SODIUM MALONATE, AFTER CATALYSIS IN THE CRYSTAL (2.3 A RESOLUTION)==
-The line below this paragraph, containing "STRUCTURE_1n5l", creates the "Structure Box" on the page.
+<StructureSection load='1n5l' size='340' side='right'caption='[[1n5l]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<table><tr><td colspan='2'>[[1n5l]] 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=1N5L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1N5L FirstGlance]. <br>
-or leave the SCENE parameter empty for the default display.
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3&#8491;</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=DPO:DIPHOSPHATE'>DPO</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=TMP:THYMIDINE-5-PHOSPHATE'>TMP</scene>, <scene name='pdbligand=TYD:THYMIDINE-5-DIPHOSPHATE'>TYD</scene></td></tr>
-{{STRUCTURE_1n5l|  PDB=1n5l  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1n5l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1n5l OCA], [https://pdbe.org/1n5l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1n5l RCSB], [https://www.ebi.ac.uk/pdbsum/1n5l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1n5l 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]
+== Evolutionary Conservation ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/n5/1n5l_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </jmolCheckbox>
+</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=1n5l ConSurf].
+<div style="clear:both"></div>
-'''CRYSTAL STRUCTURE OF MYCOBACTERIUM TUBERCULOSIS THYMIDYLATE KINASE CRYSTALLIZED IN SODIUM MALONATE, AFTER CATALYSIS IN THE CRYSTAL (2.3 A RESOLUTION)'''
+==See Also==
+*[[Thymidylate kinase 3D structures|Thymidylate kinase 3D structures]]
+__TOC__
-==Overview==
+</StructureSection>
-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.
+[[Category: Large Structures]]
-==About this Structure==
-N5L is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1N5L OCA].
-==Reference==
-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:[http://www.ncbi.nlm.nih.gov/pubmed/12662932 12662932]
 [[Category: Mycobacterium tuberculosis]]
-[[Category: Single protein]]
+[[Category: Bourgeois D]]
-[[Category: DTMP kinase]]
+[[Category: Delarue M]]
-[[Category: Bourgeois, D.]]
+[[Category: Fioravanti E]]
-[[Category: Delarue, M.]]
+[[Category: Haouz A]]
-[[Category: Fioravanti, E.]]
+[[Category: Munier-Lehmann H]]
-[[Category: Haouz, A.]]
+[[Category: Ursby T]]
-[[Category: Munier-Lehmann, H.]]
-[[Category: Ursby, T.]]
-[[Category: Kinase]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 02:07:17 2008''