5xb2 | pdb_00005xb2

ADP-Mg-F-dTMP bound Crystal structure of thymidylate kinase (aq_969) from Aquifex Aeolicus VF5

spinqualitylabelsall models 5xb2, resolution 2.16Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5xb2 is a 2 chain structure with sequence from Aquae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: ADP, F, MG, TMP Related: 5xai, 5xb3, 5xb5, 5xbh Gene: tmk, aq_969 (AQUAE) Activity: dTMP kinase, with EC number 2.7.4.9 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [KTHY_AQUAE] Phosphorylation of dTMP to form dTDP in both de novo and salvage pathways of dTTP synthesis (By similarity). Publication Abstract from PubMed Thymidylate 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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