Folylpolyglutamate synthase: Difference between revisions

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Revision as of 15:57, 29 July 2021


Function

Folylpolyglutamate synthase (FPGS) is active in intracellular folate homeostasis. Polyglutamated folates are substrates for generation of the primary metyhl group donor S-adenosylmethionine (SAM)[1].

Disease

Mutations in FPGS are associated with increased childhood acute lymphoblastic leukemia[2].

Relevance

FPGS status is a predictor of chemosensitivity of colon cancer cells to 5-fluorouracil and methotrexate based chemotherapy and FPGS gene transfer may increase the sensitivity of colon cancer cells to 5-FU-based chemotherapy[3].

Structural highlights

The nucleotide-binding pocket of FPGS occupies a of the protein and [4]. Water molecules shown as red spheres.

Folylpolyglutamate synthase complex with AMPPCP and Co+2 ion (pink) (PDB code 2vor)

Drag the structure with the mouse to rotate

3D structures of folylpolyglutamate synthase3D structures of folylpolyglutamate synthase

Updated on 29-July-2021

ReferencesReferences

  1. ↑ Kim SE, Hinoue T, Kim MS, Sohn KJ, Cho RC, Weisenberger DJ, Laird PW, Kim YI. Effects of folylpolyglutamate synthase modulation on global and gene-specific DNA methylation and gene expression in human colon and breast cancer cells. J Nutr Biochem. 2016 Mar;29:27-35. doi: 10.1016/j.jnutbio.2015.10.019. Epub 2015 , Nov 17. PMID:26895662 doi:http://dx.doi.org/10.1016/j.jnutbio.2015.10.019
  2. ↑ Piwkham D, Siriboonpiputtana T, Beuten J, Pakakasama S, Gelfond JA, Paisooksantivatana K, Tomlinson GE, Rerkamnuaychoke B. Mutation Screening and Association Study of the Folylpolyglutamate Synthetase (FPGS) Gene with Susceptibility to Childhood Acute Lymphoblastic Leukemia. Asian Pac J Cancer Prev. 2015;16(11):4727-32. PMID:26107232
  3. ↑ Sohn KJ, Smirnakis F, Moskovitz DN, Novakovic P, Yates Z, Lucock M, Croxford R, Kim YI. Effects of folylpolyglutamate synthetase modulation on chemosensitivity of colon cancer cells to 5-fluorouracil and methotrexate. Gut. 2004 Dec;53(12):1825-31. PMID:15542523 doi:http://dx.doi.org/10.1136/gut.2004.042713
  4. ↑ Young PG, Smith CA, Metcalf P, Baker EN. Structures of Mycobacterium tuberculosis folylpolyglutamate synthase complexed with ADP and AMPPCP. Acta Crystallogr D Biol Crystallogr. 2008 Jul;D64(Pt 7):745-53. Epub 2008, Jun 18. PMID:18566510 doi:http://dx.doi.org/10.1107/S0907444908012262

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Michal Harel, Jaime Prilusky, Alexander Berchansky, Joel L. Sussman, Karsten Theis
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