3ob7

Human Thymidylate Synthase R163K with Cys 195 covalently modified by Glutathione

spinqualitylabelsall models 3ob7, resolution 2.75Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3ob7 is a 5 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.75Å Ligands: GSH, PO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function TYSY_HUMAN Contributes to the de novo mitochondrial thymidylate biosynthesis pathway. Publication Abstract from PubMed Thymidylate synthase (TS) is a well validated target in cancer chemotherapy. Here, a new crystal form of the R163K variant of human TS (hTS) with five subunits per asymmetric part of the unit cell, all with loop 181-197 in the active conformation, is reported. This form allows binding studies by soaking crystals in artificial mother liquors containing ligands that bind in the active site. Using this approach, crystal structures of hTS complexes with FdUMP and dUMP were obtained, indicating that this form should facilitate high-throughput analysis of hTS complexes with drug candidates. Crystal soaking experiments using oxidized glutathione revealed that hTS binds this ligand. Interestingly, the two types of binding observed are both asymmetric. In one subunit of the physiological dimer covalent modification of the catalytic nucleophile Cys195 takes place, while in another dimer a noncovalent adduct with reduced glutathione is formed in one of the active sites. Structures of human thymidylate synthase R163K with dUMP, FdUMP and glutathione show asymmetric ligand binding.,Gibson LM, Celeste LR, Lovelace LL, Lebioda L Acta Crystallogr D Biol Crystallogr. 2011 Jan;67(Pt 1):60-6. Epub 2010 Dec 16. PMID:21206062 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Thymidylate synthase 3D structures

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