Folylpolyglutamate synthase: Difference between revisions
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<StructureSection load='' size='400' side='right' caption=' | <StructureSection load='' size='400' side='right' caption='Folylpolyglutamate synthase complex with AMPPCP and Co+2 ion (pink) (PDB code [[2vor]])' scene='74/748269/Cv/1'> | ||
== Function == | == 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)<ref>PMID:26895662</ref>. | ||
== Disease == | == Disease == | ||
| Line 13: | Line 13: | ||
The nucleotide-binding pocket of FPGS occupies a <scene name='74/748269/Cv/4'>narrow channel between the N- and C-terminal domains</scene> of the protein and <scene name='74/748269/Cv/5'>contains the nucleotide and a divalent ion</scene><ref>PMID:18566510</ref>. Water molecules shown as red spheres. | The nucleotide-binding pocket of FPGS occupies a <scene name='74/748269/Cv/4'>narrow channel between the N- and C-terminal domains</scene> of the protein and <scene name='74/748269/Cv/5'>contains the nucleotide and a divalent ion</scene><ref>PMID:18566510</ref>. Water molecules shown as red spheres. | ||
</StructureSection> | </StructureSection> | ||
==3D structures of | ==3D structures of folylpolyglutamate synthase== | ||
Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}} | Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}} | ||
{{#tree:id=OrganizedByTopic|openlevels=0| | {{#tree:id=OrganizedByTopic|openlevels=0| | ||
* | *Folylpolyglutamate synthase | ||
**[[3nrs]] – YpFPGS/dihydrofolate synthase – ''Yersinia pestis'' <BR /> | **[[3nrs]] – YpFPGS/dihydrofolate synthase – ''Yersinia pestis'' <BR /> | ||
**[[1o5z]] – FPGS – ''Thermotoga maritima'' <BR /> | **[[1o5z]] – FPGS – ''Thermotoga maritima'' <BR /> | ||
**[[2gca]] – LcFPGS – ''Lactobacillus casei'' <BR /> | **[[2gca]] – LcFPGS – ''Lactobacillus casei'' <BR /> | ||
**[[6k8c]] – FPGS – ''Helicobacter pylori'' <BR /> | |||
* | *Folylpolyglutamate synthase complex | ||
**[[3qcz]] – YpFPGS/dihydrofolate synthase + AMPPNP + Mn + glutamate <BR /> | **[[3qcz]] – YpFPGS/dihydrofolate synthase + AMPPNP + Mn + glutamate <BR /> | ||
Revision as of 10:41, 29 July 2021
FunctionFolylpolyglutamate synthase (FPGS) is active in intracellular folate homeostasis. Polyglutamated folates are substrates for generation of the primary metyhl group donor S-adenosylmethionine (SAM)[1]. DiseaseMutations in FPGS are associated with increased childhood acute lymphoblastic leukemia[2]. RelevanceFPGS 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 highlightsThe nucleotide-binding pocket of FPGS occupies a of the protein and [4]. Water molecules shown as red spheres. |
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3D structures of folylpolyglutamate synthase3D structures of folylpolyglutamate synthase
Updated on 29-July-2021
ReferencesReferences
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 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