4a35

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Crystal structure of human Mitochondrial enolase superfamily member 1 (ENOSF1)Crystal structure of human Mitochondrial enolase superfamily member 1 (ENOSF1)

Structural highlights

4a35 is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[ENOF1_HUMAN] May regulate thymidylate synthase activity.[1] [2]

Publication Abstract from PubMed

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: alpha, beta, and gamma, with the transcript of the alpha-isoform overlapping with that of TS. rTSbeta 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 rTSgamma 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 rTSbeta and rTSgamma, enabling more informed proposals for the possible function of rTSbeta in chemotherapeutic resistance.

Enzymatic and structural characterization of rTSgamma provides insights into the function of rTSbeta.,Wichelecki DJ, Froese DS, Kopec J, Muniz JR, Yue WW, Gerlt JA Biochemistry. 2014 Apr 29;53(16):2732-8. doi: 10.1021/bi500349e. Epub 2014 Apr, 15. PMID:24697329[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

  1. Dolnick BJ, Black AR, Winkler PM, Schindler K, Hsueh CT. rTS gene expression is associated with altered cell sensitivity to thymidylate synthase inhibitors. Adv Enzyme Regul. 1996;36:165-80. PMID:8869746
  2. Dolnick BJ, Angelino NJ, Dolnick R, Sufrin JR. A novel function for the rTS gene. Cancer Biol Ther. 2003 Jul-Aug;2(4):364-9. PMID:14508106
  3. Wichelecki DJ, Froese DS, Kopec J, Muniz JR, Yue WW, Gerlt JA. Enzymatic and structural characterization of rTSgamma provides insights into the function of rTSbeta. Biochemistry. 2014 Apr 29;53(16):2732-8. doi: 10.1021/bi500349e. Epub 2014 Apr, 15. PMID:24697329 doi:http://dx.doi.org/10.1021/bi500349e

4a35, resolution 1.74Å

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