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| | <StructureSection load='1e98' size='340' side='right'caption='[[1e98]], [[Resolution|resolution]] 1.90Å' scene=''> | | <StructureSection load='1e98' size='340' side='right'caption='[[1e98]], [[Resolution|resolution]] 1.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1e98]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1E98 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1E98 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1e98]] 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=1E98 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1E98 FirstGlance]. <br> |
| - | </td></tr><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> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1e2d|1e2d]], [[1e2e|1e2e]], [[1e2f|1e2f]], [[1e2g|1e2g]], [[1e2q|1e2q]], [[1e99|1e99]], [[1e9a|1e9a]], [[1e9b|1e9b]], [[1e9c|1e9c]], [[1e9d|1e9d]], [[1e9e|1e9e]], [[1e9f|1e9f]]</div></td></tr> | + | <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='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><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></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=1e98 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1e98 OCA], [https://pdbe.org/1e98 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1e98 RCSB], [https://www.ebi.ac.uk/pdbsum/1e98 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1e98 ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=1e98 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1e98 OCA], [http://pdbe.org/1e98 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1e98 RCSB], [http://www.ebi.ac.uk/pdbsum/1e98 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1e98 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/KTHY_HUMAN KTHY_HUMAN]] Catalyzes the conversion of dTMP to dTDP. | + | [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]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[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: Reintein, J]] | + | [[Category: Schlichting I]] |
| - | [[Category: Schlichting, I]] | + | [[Category: Veit T]] |
| - | [[Category: Veit, T]] | + | |
| - | [[Category: P-loop]]
| + | |
| - | [[Category: Phosphotransferase]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
KTHY_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 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.
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 Also
References
- ↑ Ostermann N, Lavie A, Padiyar S, Brundiers R, Veit T, Reinstein J, Goody RS, Konrad M, Schlichting I. 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. J Mol Biol. 2000 Nov 17;304(1):43-53. PMID:11071809 doi:10.1006/jmbi.2000.4175
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