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| | <StructureSection load='5x7j' size='340' side='right'caption='[[5x7j]], [[Resolution|resolution]] 1.84Å' scene=''> | | <StructureSection load='5x7j' size='340' side='right'caption='[[5x7j]], [[Resolution|resolution]] 1.84Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5x7j]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Thet8 Thet8]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5X7J OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5X7J FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5x7j]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Thermus_thermophilus_HB8 Thermus thermophilus HB8]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5X7J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5X7J FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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]] 1.84Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">tmk, TTHA1607 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=300852 THET8])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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=5x7j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5x7j OCA], [https://pdbe.org/5x7j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5x7j RCSB], [https://www.ebi.ac.uk/pdbsum/5x7j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5x7j ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5x7j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5x7j OCA], [http://pdbe.org/5x7j PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5x7j RCSB], [http://www.ebi.ac.uk/pdbsum/5x7j PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5x7j ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/KTHY_THET8 KTHY_THET8]] Phosphorylation of dTMP to form dTDP in both de novo and salvage pathways of dTTP synthesis. | + | [https://www.uniprot.org/uniprot/KTHY_THET8 KTHY_THET8] Phosphorylation of dTMP to form dTDP in both de novo and salvage pathways of dTTP synthesis. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 5x7j" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5x7j" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Thymidylate kinase 3D structures|Thymidylate kinase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Thet8]] | + | [[Category: Thermus thermophilus HB8]] |
| - | [[Category: DTMP kinase]]
| + | [[Category: Chaudhary SK]] |
| - | [[Category: Chaudhary, S K]] | + | [[Category: Jeyakanthan J]] |
| - | [[Category: Jeyakanthan, J]] | + | [[Category: Sekar K]] |
| - | [[Category: Sekar, K]] | + | |
| - | [[Category: Nmp kinase]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
KTHY_THET8 Phosphorylation of dTMP to form dTDP in both de novo and salvage pathways of dTTP synthesis.
Publication Abstract from PubMed
Several studies on enzyme catalysis have pointed out that the product release event could be a rate limiting step. In this study, we have compared the release event of two products, Adenosine di-phosphate (ADP) and Thymidine di-phosphate (TDP) from the active-site of human and Thermus thermophilus thymidine mono-phosphate kinase (TMPK), referred to as hTMPK and ttTMPK, respectively. TMPK catalyses the conversion of Thymidine mono-phosphate (TMP) to TDP using ATP as phosphoryl donor in the presence of Mg(2+) ion. Most of the earlier studies on this enzyme have focused on understanding substrate binding and catalysis, but the critical product release event remains elusive. Competitive binding experiments of the substrates and the products using ttTMPK apo crystals have indicated that the substrate (TMP) can replace the bound product (TDP), even in the presence of an ADP molecule. Further, the existing random accelerated molecular dynamics (RAMD) simulation program was modified to study the release of both the products simultaneously from the active site. The RAMD simulations on product-bound structures of both ttTMPK and hTMPK, revealed that while several exit patterns of the products are permissible, the sequential exit mode is the most preferred pattern for both ttTMPK and hTMPK enzymes. Additionally, the product release from the hTMPK was found to be faster and more directional as compared to ttTMPK. Structural investigation revealed that the critical changes in the residue composition in the LID-region of ttTMPK and hTMPK have an effect on the product release and can be attributed to the observed differences during product release event. Understanding of these dissimilarities is of considerable utility in designing potent inhibitors or prodrugs that can distinguish between eukaryotic and prokaryotic homologues of thymidylate kinase.
Insights into product release dynamics through structural analyses of thymidylate kinase.,Chaudhary SK, Iyyappan Y, Elayappan M, Jeyakanthan J, Sekar K Int J Biol Macromol. 2018 Nov 14;123:637-647. doi:, 10.1016/j.ijbiomac.2018.11.025. PMID:30447376[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Chaudhary SK, Iyyappan Y, Elayappan M, Jeyakanthan J, Sekar K. Insights into product release dynamics through structural analyses of thymidylate kinase. Int J Biol Macromol. 2018 Nov 14;123:637-647. doi:, 10.1016/j.ijbiomac.2018.11.025. PMID:30447376 doi:http://dx.doi.org/10.1016/j.ijbiomac.2018.11.025
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