Folylpolyglutamate synthase

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<StructureSection load='2vor' size='340' side='right' caption='Folypolyglutamate synthase complex with ADP, AMPPCP and Co+2 ion (pink) (PDB code [[2vor]]' scene=''>
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<StructureSection load='2vor' size='340' side='right' caption='Folypolyglutamate synthase complex with ADP, AMPPCP and Co+2 ion (pink) (PDB code [[2vor]])' scene=''>
== Function ==
== Function ==
'''Folypolyglutamate synthase''' (FPGS) is active in intracellular folate homeostasis. Polyglutamated folates are substrates for generation of the primary metyhl group donor S-adenosylmethionine (SAM)<ref>PMID:26895662</ref>.
'''Folypolyglutamate synthase''' (FPGS) is active in intracellular folate homeostasis. Polyglutamated folates are substrates for generation of the primary metyhl group donor S-adenosylmethionine (SAM)<ref>PMID:26895662</ref>.
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== Disease ==
== Disease ==
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Mutations in FPGS are associated with increased childhood acute lymphoblastic leukemia<ref>PMID:26107232</ref>.
== Relevance ==
== 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<ref>PMID:15542523</ref>.
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<ref>PMID:15542523</ref>.
== Structural highlights ==
== Structural highlights ==
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The nucleotide -binding pocket of FPGS occupies a narrow channel between the N- and C-terminal domains of the protein and contains the nucleotide and a divalent ion<ref>PMID:18566510</ref>.
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This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.
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</StructureSection>
</StructureSection>
==3D structures of folypolyglutamate synthase==
==3D structures of folypolyglutamate synthase==

Revision as of 11:13, 15 December 2016

Folypolyglutamate synthase complex with ADP, AMPPCP and Co+2 ion (pink) (PDB code 2vor)

Drag the structure with the mouse to rotate

3D structures of folypolyglutamate synthase

Updated on 15-December-2016

References

  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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