4gte

T. Maritima FDTS (E144R mutant) with FAD and Folate

spinqualitylabelsall models 4gte, resolution 1.89Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4gte is a 4 chain structure with sequence from Thermotoga maritima msb8. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: FAD, MEF Gene: thyX, thy1, TM_0449 (Thermotoga maritima MSB8) Activity: Thymidylate synthase (FAD), with EC number 2.1.1.148 Resources: FirstGlance, OCA, RCSB, PDBsum Function [THYX_THEMA] Catalyzes the formation of dTMP and tetrahydrofolate from dUMP and methylenetetrahydrofolate. Publication Abstract from PubMed The DNA nucleotide thymidylate is synthesized by the enzyme thymidylate synthase, which catalyzes the reductive methylation of deoxyuridylate using the cofactor methylene-tetrahydrofolate (CH(2)H(4)folate). Most organisms, including humans, rely on the thyA- or TYMS-encoded classic thymidylate synthase, whereas, certain microorganisms, including all Rickettsia and other pathogens, use an alternative thyX-encoded flavin-dependent thymidylate synthase (FDTS). Although several crystal structures of FDTSs have been reported, the absence of a structure with folates limits understanding of the molecular mechanism and the scope of drug design for these enzymes. Here we present X-ray crystal structures of FDTS with several folate derivatives, which together with mutagenesis, kinetic analysis, and computer modeling shed light on the cofactor binding and function. The unique structural data will likely facilitate further elucidation of FDTSs' mechanism and the design of structure-based inhibitors as potential leads to new antimicrobial drugs. Folate binding site of flavin-dependent thymidylate synthase.,Koehn EM, Perissinotti LL, Moghram S, Prabhakar A, Lesley SA, Mathews II, Kohen A Proc Natl Acad Sci U S A. 2012 Sep 25;109(39):15722-7. Epub 2012 Sep 10. PMID:23019356 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Thymidylate synthase

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