1e9c

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[[Image:1e9c.jpg|left|200px]]
 
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{{Structure
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==Mutant human thymidylate kinase complexed with TMP and APPNP==
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|PDB= 1e9c |SIZE=350|CAPTION= <scene name='initialview01'>1e9c</scene>, resolution 1.6&Aring;
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<StructureSection load='1e9c' size='340' side='right'caption='[[1e9c]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
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|SITE= <scene name='pdbsite=TMP:Anp+Binding+Site'>TMP</scene>
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== Structural highlights ==
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|LIGAND= <scene name='pdbligand=ADP:ADENOSINE-5&#39;-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=TMP:THYMIDINE-5&#39;-PHOSPHATE'>TMP</scene>
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<table><tr><td colspan='2'>[[1e9c]] 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=1E9C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1E9C FirstGlance]. <br>
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|ACTIVITY= <span class='plainlinks'>[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] </span>
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</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>
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|GENE=
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=TMP:THYMIDINE-5-PHOSPHATE'>TMP</scene></td></tr>
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|DOMAIN=
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1e9c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1e9c OCA], [https://pdbe.org/1e9c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1e9c RCSB], [https://www.ebi.ac.uk/pdbsum/1e9c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1e9c ProSAT]</span></td></tr>
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|RELATEDENTRY=
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</table>
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1e9c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1e9c OCA], [http://www.ebi.ac.uk/pdbsum/1e9c PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1e9c RCSB]</span>
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== Function ==
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}}
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[https://www.uniprot.org/uniprot/KTHY_HUMAN KTHY_HUMAN] Catalyzes the conversion of dTMP to dTDP.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/e9/1e9c_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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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=1e9c ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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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.
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'''MUTANT HUMAN THYMIDYLATE KINASE COMPLEXED WITH TMP AND APPNP'''
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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>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 1e9c" style="background-color:#fffaf0;"></div>
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==Overview==
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==See Also==
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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.
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*[[Thymidylate kinase 3D structures|Thymidylate kinase 3D structures]]
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== References ==
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==About this Structure==
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<references/>
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1E9C 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=1E9C OCA].
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__TOC__
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</StructureSection>
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==Reference==
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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]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: dTMP kinase]]
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[[Category: Brundiers R]]
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[[Category: Brundiers, R.]]
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[[Category: Goody RS]]
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[[Category: Goody, R S.]]
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[[Category: Konrad M]]
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[[Category: Konrad, M.]]
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[[Category: Lavie A]]
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[[Category: Lavie, A.]]
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[[Category: Ostermann N]]
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[[Category: Ostermann, N.]]
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[[Category: Padiyar S]]
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[[Category: Padiyar, S.]]
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[[Category: Reintein J]]
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[[Category: Reinstein, J.]]
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[[Category: Schlichting I]]
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[[Category: Schlichting, I.]]
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[[Category: Veit T]]
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[[Category: Veit, T.]]
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[[Category: p-loop]]
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[[Category: thymidylate kinase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 19:57:55 2008''
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Current revision

Mutant human thymidylate kinase complexed with TMP and APPNP

PDB ID 1e9c

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