4up1

Crystal structure of native human Thymidylate synthase in active form

spinqualitylabelsall models 4up1, resolution 2.99Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4up1 is a 4 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: SO4 Related: 4up2 Activity: Thymidylate synthase, with EC number 2.1.1.45 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [TYSY_HUMAN] Contributes to the de novo mitochondrial thymidylate biosynthesis pathway. Publication Abstract from PubMed Human thymidylate synthase (hTS) provides the sole de novo intracellular source of thymidine 5'-monophosphate (dTMP). hTS is required for DNA replication prior to cell division, making it an attractive target for anticancer chemotherapy and drug discovery. hTS binds 2'-deoxyuridine 5'-monophosphate (dUMP) and the folate co-substrate N5,N10-methylenetetrahydrofolate (meTHF) in a pocket near the catalytic residue Cys195. The catalytic loop, which is composed of amino-acid residues 181-197, can adopt two distinct conformations related by a 180 degrees rotation. In the active conformation Cys195 is close to the active site, while in the inactive conformation it is rotated and Cys195 is too distant from the active site for catalysis. Several hTS structures, either native or engineered, have been solved in the active conformation in complex with ligands or inhibitors and at different salt concentrations. However, apo hTS structures have been solved in an inactive conformation in high-salt and low-salt conditions (PDB entries 1ypv, 4h1i, 4gyh, 3egy and 3ehi). Here, the structure of apo hTS crystallized in the active form with sulfate ions coordinated by the arginine residue that binds dUMP is reported. Crystal structure of the active form of native human thymidylate synthase in the absence of bound substrates.,Deschamps P, Rety S, Bareille J, Leulliot N Acta Crystallogr F Struct Biol Commun. 2017 Jun 1;73(Pt 6):336-341. doi:, 10.1107/S2053230X17007233. Epub 2017 May 25. PMID:28580921 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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