1e9a: Difference between revisions

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-[[Image:1e9a.jpg|left|200px]]
-<!--
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-{{STRUCTURE_1e9a|  PDB=1e9a  |  SCENE=  }}
-'''HUMAN THYMIDYLATE KINASE COMPLEXED WITH THE BISUBSTRATE INHIBITOR AZTP5A'''
+==Human thymidylate kinase complexed with the bisubstrate inhibitor AZTP5A==
+<StructureSection load='1e9a' size='340' side='right'caption='[[1e9a]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[1e9a]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1E9A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1E9A FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.6&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=Z5A:P1-(5-ADENOSYL)P5-(5-(3AZIDO-3-DEOXYTHYMIDYL))PENTAPHOSPHATE'>Z5A</scene></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=1e9a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1e9a OCA], [https://pdbe.org/1e9a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1e9a RCSB], [https://www.ebi.ac.uk/pdbsum/1e9a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1e9a ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/KTHY_HUMAN KTHY_HUMAN] Catalyzes the conversion of dTMP to dTDP.
+== 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/e9/1e9a_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=1e9a ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The 60-fold reduced phosphorylation rate of azidothymidine (AZT) monophosphate (AZTMP), the partially activated AZT metabolite, by human thymidylate kinase (TMPK) severely limits the efficacy of this anti-HIV prodrug. Crystal structures of different TMPK nucleotide complexes indicate that steric hindrance by the azido group of AZTMP prevents formation of the catalytically active closed conformation of the P-loop of TMPK. The F105Y mutant and a chimeric mutant that contains sequences of the human and Escherichia coli enzyme phosphorylate AZTMP 20-fold faster than the wild-type enzyme. The structural basis of the increased activity is assigned to stabilization of the closed P-loop conformation.
-==Overview==
+Potentiating AZT activation: structures of wild-type and mutant human thymidylate kinase suggest reasons for the mutants' improved kinetics with the HIV prodrug metabolite AZTMP.,Ostermann N, Lavie A, Padiyar S, Brundiers R, Veit T, Reinstein J, Goody RS, Konrad M, Schlichting I J Mol Biol. 2000 Nov 17;304(1):43-53. PMID:11071809<ref>PMID:11071809</ref>
-The 60-fold reduced phosphorylation rate of azidothymidine (AZT) monophosphate (AZTMP), the partially activated AZT metabolite, by human thymidylate kinase (TMPK) severely limits the efficacy of this anti-HIV prodrug. Crystal structures of different TMPK nucleotide complexes indicate that steric hindrance by the azido group of AZTMP prevents formation of the catalytically active closed conformation of the P-loop of TMPK. The F105Y mutant and a chimeric mutant that contains sequences of the human and Escherichia coli enzyme phosphorylate AZTMP 20-fold faster than the wild-type enzyme. The structural basis of the increased activity is assigned to stabilization of the closed P-loop conformation.
-==About this Structure==
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-E9A is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1E9A OCA].
+</div>
+<div class="pdbe-citations 1e9a" style="background-color:#fffaf0;"></div>
-==Reference==
+==See Also==
-Potentiating AZT activation: structures of wild-type and mutant human thymidylate kinase suggest reasons for the mutants' improved kinetics with the HIV prodrug metabolite AZTMP., Ostermann N, Lavie A, Padiyar S, Brundiers R, Veit T, Reinstein J, Goody RS, Konrad M, Schlichting I, J Mol Biol. 2000 Nov 17;304(1):43-53. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/11071809 11071809]
+*[[Thymidylate kinase 3D structures|Thymidylate kinase 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Single protein]]
+[[Category: Large Structures]]
-[[Category: DTMP kinase]]
+[[Category: Brundiers R]]
-[[Category: Brundiers, R.]]
+[[Category: Goody RS]]
-[[Category: Goody, R S.]]
+[[Category: Konrad M]]
-[[Category: Konrad, M.]]
+[[Category: Lavie A]]
-[[Category: Lavie, A.]]
+[[Category: Ostermann N]]
-[[Category: Ostermann, N.]]
+[[Category: Padiyar S]]
-[[Category: Padiyar, S.]]
+[[Category: Reintein J]]
-[[Category: Reinstein, J.]]
+[[Category: Schlichting I]]
-[[Category: Schlichting, I.]]
+[[Category: Veit T]]
-[[Category: Veit, T.]]
-[[Category: P-loop]]
-[[Category: Thymidylate kinase]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May  2 14:49:32 2008''