1e9d: Difference between revisions
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==Mutant human thymidylate kinase (F105Y) complexed with AZTMP and ADP== | ==Mutant human thymidylate kinase (F105Y) complexed with AZTMP and ADP== | ||
<StructureSection load='1e9d' size='340' side='right' caption='[[1e9d]], [[Resolution|resolution]] 1.70Å' scene=''> | <StructureSection load='1e9d' size='340' side='right'caption='[[1e9d]], [[Resolution|resolution]] 1.70Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[1e9d]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1E9D OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[1e9d]] 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=1E9D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1E9D FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.7Å</td></tr> | ||
<tr id=' | <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=ATM:3-AZIDO-3-DEOXYTHYMIDINE-5-MONOPHOSPHATE'>ATM</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=1e9d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1e9d OCA], [https://pdbe.org/1e9d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1e9d RCSB], [https://www.ebi.ac.uk/pdbsum/1e9d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1e9d ProSAT]</span></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/KTHY_HUMAN KTHY_HUMAN] Catalyzes the conversion of dTMP to dTDP. | |||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
Check<jmol> | Check<jmol> | ||
<jmolCheckbox> | <jmolCheckbox> | ||
<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/e9/1e9d_consurf.spt"</scriptWhenChecked> | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/e9/1e9d_consurf.spt"</scriptWhenChecked> | ||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
<text>to colour the structure by Evolutionary Conservation</text> | <text>to colour the structure by Evolutionary Conservation</text> | ||
| Line 30: | Line 31: | ||
==See Also== | ==See Also== | ||
*[[Thymidylate kinase|Thymidylate kinase]] | *[[Thymidylate kinase 3D structures|Thymidylate kinase 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: Brundiers | [[Category: Large Structures]] | ||
[[Category: Goody | [[Category: Brundiers R]] | ||
[[Category: Konrad | [[Category: Goody RS]] | ||
[[Category: Lavie | [[Category: Konrad M]] | ||
[[Category: Ostermann | [[Category: Lavie A]] | ||
[[Category: Padiyar | [[Category: Ostermann N]] | ||
[[Category: Reintein | [[Category: Padiyar S]] | ||
[[Category: Schlichting | [[Category: Reintein J]] | ||
[[Category: Veit | [[Category: Schlichting I]] | ||
[[Category: Veit T]] | |||
Latest revision as of 11:48, 9 May 2024
Mutant human thymidylate kinase (F105Y) complexed with AZTMP and ADPMutant human thymidylate kinase (F105Y) complexed with AZTMP and ADP
Structural highlights
FunctionKTHY_HUMAN Catalyzes the conversion of dTMP to dTDP. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe 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. 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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