Substrate Activation in Flavin-Dependent Thymidylate Synthase
نویسندگان
چکیده
منابع مشابه
Substrate Activation in Flavin-Dependent Thymidylate Synthase
Thymidylate is a critical DNA nucleotide that has to be synthesized in cells de novo by all organisms. Flavin-dependent thymidylate synthase (FDTS) catalyzes the final step in this de novo production of thymidylate in many human pathogens, but it is absent from humans. The FDTS reaction proceeds via a chemical route that is different from its human enzyme analogue, making FDTS a potential antim...
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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 altern...
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Here we report on a Chlamydia trachomatis gene that complements the growth defect of a thymidylate synthase-deficient strain of Escherichia coli. The complementing gene encodes a 60.9-kDa protein that shows low level primary sequence homology to a new class of thymidylate-synthesizing enzymes, termed flavin-dependent thymidylate synthases (FDTS). Purified recombinant chlamydial FDTS (CTThyX) co...
متن کاملFlavin dependent thymidylate synthase as a new antibiotic target
In humans de novo synthesis of 2'-deoxythymidine-5'-monophosphate (dTMP), an essential building block of DNA, utilizes an enzymatic pathway requiring thymidylate synthase (TSase) and dihydrofolate reductase (DHFR). The enzyme flavin-dependent thymidylate synthase (FDTS) represents an alternative enzymatic pathway to synthesize dTMP, which is not present in human cells. A number of pathogenic ba...
متن کاملAccelerated Publications Mechanistic Studies of a Flavin-Dependent Thymidylate Synthase†
The ThyA gene that encodes for thymidylate synthase (TS) is absent in the genomes of a large number of bacteria, including several human pathogens. Many of these bacteria also lack the genes for dihydrofolate reductase (DHFR) and thymidine kinase and are totally dependent on an alternative enzyme for thymidylate synthesis. Thy1 encodes flavin-dependent TS (FDTS, previously denoted as TSCP) and ...
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ژورنال
عنوان ژورنال: Journal of the American Chemical Society
سال: 2014
ISSN: 0002-7863,1520-5126
DOI: 10.1021/ja506108b