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Enzymatic and structural characterization of rTS? provides insights into the function of rTS?.

ABSTRACT: In humans, the gene encoding a reverse thymidylate synthase (rTS) is transcribed in the reverse direction of the gene encoding thymidylate synthase (TS) that is involved in DNA biosynthesis. Three isoforms are found: ?, ?, and ?, with the transcript of the ?-isoform overlapping with that of TS. rTS? has been of interest since the discovery of its overexpression in methotrexate and 5-fluorouracil resistant cell lines. Despite more than 20 years of study, none of the rTS isoforms have been biochemically or structurally characterized. In this study, we identified rTS? as an l-fuconate dehydratase and determined its high-resolution crystal structure. Our data provide an explanation for the observed difference in enzymatic activities between rTS? and rTS?, enabling more informed proposals for the possible function of rTS? in chemotherapeutic resistance.

SUBMITTER: Wichelecki DJ

PROVIDER: S-EPMC4010280 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

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Enzymatic and structural characterization of rTSγ provides insights into the function of rTSβ.

Wichelecki Daniel J DJ Froese D Sean DS Kopec Jolanta J Muniz Joao R C JR Yue Wyatt W WW Gerlt John A JA

Biochemistry 20140415 16

In humans, the gene encoding a reverse thymidylate synthase (rTS) is transcribed in the reverse direction of the gene encoding thymidylate synthase (TS) that is involved in DNA biosynthesis. Three isoforms are found: α, β, and γ, with the transcript of the α-isoform overlapping with that of TS. rTSβ has been of interest since the discovery of its overexpression in methotrexate and 5-fluorouracil resistant cell lines. Despite more than 20 years of study, none of the rTS isoforms have been biochem ...[more]

PMID: 24697329

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