5h5b: Difference between revisions
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<StructureSection load='5h5b' size='340' side='right'caption='[[5h5b]], [[Resolution|resolution]] 2.05Å' scene=''> | <StructureSection load='5h5b' size='340' side='right'caption='[[5h5b]], [[Resolution|resolution]] 2.05Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5h5b]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5H5B OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[5h5b]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Aquifex_aeolicus_VF5 Aquifex aeolicus VF5]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5H5B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5H5B 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]] 2.05Å</td></tr> | ||
<tr id=' | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FLC:CITRATE+ANION'>FLC</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=5h5b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5h5b OCA], [https://pdbe.org/5h5b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5h5b RCSB], [https://www.ebi.ac.uk/pdbsum/5h5b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5h5b ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/KTHY_AQUAE KTHY_AQUAE] Phosphorylation of dTMP to form dTDP in both de novo and salvage pathways of dTTP synthesis (By similarity). | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Aquifex aeolicus VF5]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Biswas A]] | |||
[[Category: Biswas | [[Category: Jeyakanthan J]] | ||
[[Category: Jeyakanthan | [[Category: Sekar K]] | ||
[[Category: Sekar | |||
Latest revision as of 10:23, 9 August 2023
Citrate ion bound crystal structure of thymidylate kinase (aq_969) from Aquifex Aeolicus VF5Citrate ion bound crystal structure of thymidylate kinase (aq_969) from Aquifex Aeolicus VF5
Structural highlights
FunctionKTHY_AQUAE Phosphorylation of dTMP to form dTDP in both de novo and salvage pathways of dTTP synthesis (By similarity). Publication Abstract from PubMedThymidylate kinase (TMK) is a key enzyme which plays an important role in DNA synthesis. It belongs to the family of nucleoside monophosphate kinases, several of which undergo structure-encoded conformational changes to perform their function. However, the absence of three-dimensional structures for all the different reaction intermediates of a single TMK homolog hinders a clear understanding of its functional mechanism. We herein report the different conformational states along the reaction coordinate of a hyperthermophilic TMK from Aquifex aeolicus, determined via X-ray diffraction and further validated through normal-mode studies. The analyses implicate an arginine residue in the Lid region in catalysis, which was confirmed through site-directed mutagenesis and subsequent enzyme assays on the wild-type protein and mutants. Furthermore, the enzyme was found to exhibit broad specificity toward phosphate group acceptor nucleotides. Our comprehensive analyses of the conformational landscape of TMK, together with associated biochemical experiments, provide insights into the mechanistic details of TMK-driven catalysis, for example, the order of substrate binding and the reaction mechanism for phosphate transfer. Such a study has utility in the design of potent inhibitors for these enzymes. DATABASE: Structural data are available in the PDB under the accession numbers 2PBR, 4S2E, 5H5B, 5XAI, 4S35, 5XB2, 5H56, 5XB3, 5H5K, 5XB5, and 5XBH. Structural studies of a hyperthermophilic thymidylate kinase enzyme reveal conformational substates along the reaction coordinate.,Biswas A, Shukla A, Chaudhary SK, Santhosh R, Jeyakanthan J, Sekar K FEBS J. 2017 Aug;284(15):2527-2544. doi: 10.1111/febs.14140. Epub 2017 Jul 13. PMID:28627020[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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