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| | ==FPGS-AMPPCP-folate complex== | | ==FPGS-AMPPCP-folate complex== |
| - | <StructureSection load='1jbw' size='340' side='right' caption='[[1jbw]], [[Resolution|resolution]] 1.85Å' scene=''> | + | <StructureSection load='1jbw' size='340' side='right'caption='[[1jbw]], [[Resolution|resolution]] 1.85Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1jbw]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_a"_von_freudenreich_1890 "bacillus a" von freudenreich 1890]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1JBW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1JBW FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1jbw]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Lacticaseibacillus_casei Lacticaseibacillus casei]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1JBW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1JBW FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACQ:DIPHOSPHOMETHYLPHOSPHONIC+ACID+ADENYLATE+ESTER'>ACQ</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=TMF:5,10-METHYLENE-6-HYDROFOLIC+ACID'>TMF</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.85Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=KCX:LYSINE+NZ-CARBOXYLIC+ACID'>KCX</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACQ:DIPHOSPHOMETHYLPHOSPHONIC+ACID+ADENYLATE+ESTER'>ACQ</scene>, <scene name='pdbligand=KCX:LYSINE+NZ-CARBOXYLIC+ACID'>KCX</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=TMF:5,10-METHYLENE-6-HYDROFOLIC+ACID'>TMF</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1fgs|1fgs]], [[1jbv|1jbv]]</td></tr>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1jbw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1jbw OCA], [https://pdbe.org/1jbw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1jbw RCSB], [https://www.ebi.ac.uk/pdbsum/1jbw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1jbw ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Tetrahydrofolate_synthase Tetrahydrofolate synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.3.2.17 6.3.2.17] </span></td></tr>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1jbw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1jbw OCA], [http://pdbe.org/1jbw PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1jbw RCSB], [http://www.ebi.ac.uk/pdbsum/1jbw PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1jbw ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/FOLC_LACCA FOLC_LACCA]] Conversion of folates to polyglutamate derivatives. It prefers 5,10-methylenetetrahydrofolate, rather than 10-formyltetrahydrofolate as folate substrate. | + | [https://www.uniprot.org/uniprot/FPGS_LACCA FPGS_LACCA] Involved in the conversion of folates to polyglutamate derivatives, and likely functions in the retention of cellular folate pools. Catalyzes successive MgATP-dependent additions of glutamate to a pteroylmonoglutamate substrate, with a high preference for 5,10-methylenetetrahydrofolate (mTHF). Thus, metabolizes mTHF to the tetraglutamate derivative, but longer glutamate chain length products are not observed. Tetrahydrofolate (H4PteGlu) and 10-formyl-H4PteGlu are poorer folate substrates. In contrast to E.coli FolC, this enzyme does not display dihydrofolate synthase activity.<ref>PMID:18232714</ref> <ref>PMID:6138353</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | <jmolCheckbox> | | <jmolCheckbox> |
| | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/jb/1jbw_consurf.spt"</scriptWhenChecked> | | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/jb/1jbw_consurf.spt"</scriptWhenChecked> |
| - | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> | | </jmolCheckbox> |
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| | </div> | | </div> |
| | <div class="pdbe-citations 1jbw" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 1jbw" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Folylpolyglutamate synthase|Folylpolyglutamate synthase]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Bacillus a von freudenreich 1890]] | + | [[Category: Lacticaseibacillus casei]] |
| - | [[Category: Tetrahydrofolate synthase]] | + | [[Category: Large Structures]] |
| - | [[Category: Baker, E N]] | + | [[Category: Baker EN]] |
| - | [[Category: Bognar, A L]] | + | [[Category: Bognar AL]] |
| - | [[Category: Cross, J A]] | + | [[Category: Cross JA]] |
| - | [[Category: Smith, C A]] | + | [[Category: Smith CA]] |
| - | [[Category: Sun, X]] | + | [[Category: Sun X]] |
| - | [[Category: Fpgs folate amppcp ternary complex]]
| + | |
| - | [[Category: Ligase]]
| + | |
| Structural highlights
Function
FPGS_LACCA Involved in the conversion of folates to polyglutamate derivatives, and likely functions in the retention of cellular folate pools. Catalyzes successive MgATP-dependent additions of glutamate to a pteroylmonoglutamate substrate, with a high preference for 5,10-methylenetetrahydrofolate (mTHF). Thus, metabolizes mTHF to the tetraglutamate derivative, but longer glutamate chain length products are not observed. Tetrahydrofolate (H4PteGlu) and 10-formyl-H4PteGlu are poorer folate substrates. In contrast to E.coli FolC, this enzyme does not display dihydrofolate synthase activity.[1] [2]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Folic acid is an essential vitamin for normal cell growth, primarily through its central role in one-carbon metabolism. Folate analogs (antifolates) are targeted at the same reactions and are widely used as therapeutic drugs for cancer and bacterial infections. Effective retention of folates in cells and the efficacy of antifolate drugs both depend upon the addition of a polyglutamate tail to the folate or antifolate molecule by the enzyme folylpolyglutamate synthetase (FPGS). The reaction mechanism involves the ATP-dependent activation of the free carboxylate group on the folate molecule to give an acyl phosphate intermediate, followed by attack by the incoming L-glutamate substrate. FPGS shares a number of structural and mechanistic details with the bacterial cell wall ligases MurD, MurE and MurF, and these enzymes, along with FPGS, form a subfamily of the ADP-forming amide bond ligase family. High-resolution crystallographic analyses of binary and ternary complexes of Lactobacillus casei FPGS reveal that binding of the first substrate (ATP) is not sufficient to generate an active enzyme. However, binding of folate as the second substrate triggers a large conformational change that activates FPGS and allows the enzyme to adopt a form that is then able to bind the third substrate, L-glutamate, and effect the addition of a polyglutamate tail to the folate.
Folate-binding triggers the activation of folylpolyglutamate synthetase.,Sun X, Cross JA, Bognar AL, Baker EN, Smith CA J Mol Biol. 2001 Jul 27;310(5):1067-78. PMID:11501996[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Sheng Y, Khanam N, Tsaksis Y, Shi XM, Lu QS, Bognar AL. Mutagenesis of folylpolyglutamate synthetase indicates that dihydropteroate and tetrahydrofolate bind to the same site. Biochemistry. 2008 Feb 26;47(8):2388-96. PMID:18232714 doi:10.1021/bi701670y
- ↑ Bognar AL, Shane B. Purification and properties of Lactobacillus casei folylpoly-gamma-glutamate synthetase. J Biol Chem. 1983 Oct 25;258(20):12574-81 PMID:6138353
- ↑ Sun X, Cross JA, Bognar AL, Baker EN, Smith CA. Folate-binding triggers the activation of folylpolyglutamate synthetase. J Mol Biol. 2001 Jul 27;310(5):1067-78. PMID:11501996 doi:10.1006/jmbi.2001.4815
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