5zb4: Difference between revisions
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==Crystal structure of thymidylate kinase in complex with ADP and TMP from thermus thermophilus HB8== | |||
<StructureSection load='5zb4' size='340' side='right'caption='[[5zb4]], [[Resolution|resolution]] 1.92Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5zb4]] 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=5ZB4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5ZB4 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]] 1.92Å</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=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=TMP:THYMIDINE-5-PHOSPHATE'>TMP</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=5zb4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5zb4 OCA], [https://pdbe.org/5zb4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5zb4 RCSB], [https://www.ebi.ac.uk/pdbsum/5zb4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5zb4 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[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;"> | |||
== 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<ref>PMID:30447376</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 5zb4" style="background-color:#fffaf0;"></div> | ||
[[Category: | |||
[[Category: Jeyakanthan | ==See Also== | ||
*[[Thymidylate kinase 3D structures|Thymidylate kinase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Thermus thermophilus HB8]] | |||
[[Category: Chaudhary SK]] | |||
[[Category: Jeyakanthan J]] | |||
[[Category: Sekar K]] | |||