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| | <StructureSection load='4r8v' size='340' side='right'caption='[[4r8v]], [[Resolution|resolution]] 2.20Å' scene=''> | | <StructureSection load='4r8v' size='340' side='right'caption='[[4r8v]], [[Resolution|resolution]] 2.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4r8v]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Brachidanio_rerio Brachidanio rerio]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4R8V OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4R8V FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4r8v]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Danio_rerio Danio rerio]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4R8V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4R8V FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BTB:2-[BIS-(2-HYDROXY-ETHYL)-AMINO]-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>BTB</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BTB:2-[BIS-(2-HYDROXY-ETHYL)-AMINO]-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>BTB</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4ts4|4ts4]], [[4tt8|4tt8]], [[4qpd|4qpd]], [[4qpc|4qpc]], [[4tts|4tts]]</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=4r8v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4r8v OCA], [https://pdbe.org/4r8v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4r8v RCSB], [https://www.ebi.ac.uk/pdbsum/4r8v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4r8v ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">aldh1l1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=7955 Brachidanio rerio])</td></tr>
| + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Formyltetrahydrofolate_dehydrogenase Formyltetrahydrofolate dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.5.1.6 1.5.1.6] </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=4r8v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4r8v OCA], [http://pdbe.org/4r8v PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4r8v RCSB], [http://www.ebi.ac.uk/pdbsum/4r8v PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4r8v ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/E3NZ06_DANRE E3NZ06_DANRE] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Brachidanio rerio]] | + | [[Category: Danio rerio]] |
| - | [[Category: Formyltetrahydrofolate dehydrogenase]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Chang, W N]] | + | [[Category: Chang WN]] |
| - | [[Category: Chen, C J]] | + | [[Category: Chen CJ]] |
| - | [[Category: Chuankhayan, P]] | + | [[Category: Chuankhayan P]] |
| - | [[Category: Fu, T F]] | + | [[Category: Fu TF]] |
| - | [[Category: Kao, T T]] | + | [[Category: Kao TT]] |
| - | [[Category: Lin, C C]] | + | [[Category: Lin CC]] |
| - | [[Category: 10-formyltetrahydrofolate dehydrogenase]]
| + | |
| - | [[Category: Catalysis]]
| + | |
| - | [[Category: Hydrolase domain]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| Structural highlights
Function
E3NZ06_DANRE
Publication Abstract from PubMed
10-Formyltetrahydrofolate dehydrogenase (FDH), which is composed of a small N-terminal domain (Nt-FDH) and a large C-terminal domain, is an abundant folate enzyme in the liver and converts 10-formyltetrahydrofolate (10-FTHF) to tetrahydrofolate (THF) and CO2. Nt-FDH alone possesses a hydrolase activity, which converts 10-FTHF to THF and formate in the presence of beta-mercaptoethanol. To elucidate the catalytic mechanism of Nt-FDH, crystal structures of apo-form zNt-FDH from zebrafish and its complexes with the substrate analogue 10-formyl-5,8-dideazafolate (10-FDDF) and with the products THF and formate have been determined. The structures reveal that the conformations of three loops (residues 86-90, 135-143 and 200-203) are altered upon ligand (10-FDDF or THF) binding in the active site. The orientations and geometries of key residues, including Phe89, His106, Arg114, Asp142 and Tyr200, are adjusted for substrate binding and product release during catalysis. Among them, Tyr200 is especially crucial for product release. An additional potential THF binding site is identified in the cavity between two zNt-FDH molecules, which might contribute to the properties of product inhibition and THF storage reported for FDH. Together with mutagenesis studies and activity assays, the structures of zNt-FDH and its complexes provide a coherent picture of the active site and a potential THF binding site of zNt-FDH along with the substrate and product specificity, lending new insights into the molecular mechanism underlying the enzymatic properties of Nt-FDH.
Structures of the hydrolase domain of zebrafish 10-formyltetrahydrofolate dehydrogenase and its complexes reveal a complete set of key residues for hydrolysis and product inhibition.,Lin CC, Chuankhayan P, Chang WN, Kao TT, Guan HH, Fun HK, Nakagawa A, Fu TF, Chen CJ Acta Crystallogr D Biol Crystallogr. 2015 Apr;71(Pt 4):1006-21. doi:, 10.1107/S1399004715002928. Epub 2015 Mar 27. PMID:25849409[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Lin CC, Chuankhayan P, Chang WN, Kao TT, Guan HH, Fun HK, Nakagawa A, Fu TF, Chen CJ. Structures of the hydrolase domain of zebrafish 10-formyltetrahydrofolate dehydrogenase and its complexes reveal a complete set of key residues for hydrolysis and product inhibition. Acta Crystallogr D Biol Crystallogr. 2015 Apr;71(Pt 4):1006-21. doi:, 10.1107/S1399004715002928. Epub 2015 Mar 27. PMID:25849409 doi:http://dx.doi.org/10.1107/S1399004715002928
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