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| | <StructureSection load='5ebu' size='340' side='right'caption='[[5ebu]], [[Resolution|resolution]] 2.60Å' scene=''> | | <StructureSection load='5ebu' size='340' side='right'caption='[[5ebu]], [[Resolution|resolution]] 2.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5ebu]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/"gaffkya_homari"_hitchner_and_snieszko_1947 "gaffkya homari" hitchner and snieszko 1947]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5EBU OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5EBU FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5ebu]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Aerococcus_viridans Aerococcus viridans]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5EBU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5EBU FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FMN:FLAVIN+MONONUCLEOTIDE'>FMN</scene>, <scene name='pdbligand=PYR:PYRUVIC+ACID'>PYR</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]] 2.6Å</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5ebu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ebu OCA], [http://pdbe.org/5ebu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ebu RCSB], [http://www.ebi.ac.uk/pdbsum/5ebu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ebu ProSAT]</span></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FMN:FLAVIN+MONONUCLEOTIDE'>FMN</scene>, <scene name='pdbligand=PYR:PYRUVIC+ACID'>PYR</scene></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=5ebu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ebu OCA], [https://pdbe.org/5ebu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ebu RCSB], [https://www.ebi.ac.uk/pdbsum/5ebu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ebu ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/LOX_AERVM LOX_AERVM] Catalyzes the oxidation of (S)-lactate (L-lactate) to pyruvate, with a reduction of O2 to H2O2 (Ref.1, PubMed:27302031, PubMed:25423902, PubMed:2818595, PubMed:8589073, PubMed:26260739). Cannot oxidize D-lactate, glycolate, and D,L-2-hydroxybutanoate (PubMed:2818595). May be involved in the utilization of L-lactate as an energy source for growth (By similarity).[UniProtKB:O33655]<ref>PMID:25423902</ref> <ref>PMID:26260739</ref> <ref>PMID:27302031</ref> <ref>PMID:2818595</ref> <ref>PMID:8589073</ref> [UniProtKB:O33655] |
| | <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: Gaffkya homari hitchner and snieszko 1947]] | + | [[Category: Aerococcus viridans]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Nidetzky, B]] | + | [[Category: Nidetzky B]] |
| - | [[Category: Rainer, D]] | + | [[Category: Rainer D]] |
| - | [[Category: Wilson, D K]] | + | [[Category: Wilson DK]] |
| - | [[Category: Flavin]]
| + | |
| - | [[Category: Lactate]]
| + | |
| - | [[Category: Oxidase]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| Structural highlights
Function
LOX_AERVM Catalyzes the oxidation of (S)-lactate (L-lactate) to pyruvate, with a reduction of O2 to H2O2 (Ref.1, PubMed:27302031, PubMed:25423902, PubMed:2818595, PubMed:8589073, PubMed:26260739). Cannot oxidize D-lactate, glycolate, and D,L-2-hydroxybutanoate (PubMed:2818595). May be involved in the utilization of L-lactate as an energy source for growth (By similarity).[UniProtKB:O33655][1] [2] [3] [4] [5] [UniProtKB:O33655]
Publication Abstract from PubMed
L-Lactate oxidase (LOX) belongs to a large family of flavoenzymes that catalyze oxidation of alpha-hydroxy acids. How in these enzymes the protein structure controls reactivity presents an important but elusive problem. LOX contains a prominent tyrosine in the substrate binding pocket (Tyr(215) in Aerococcus viridans LOX) that is partially responsible for securing a flexible loop which sequesters the active site. To characterize the role of Tyr(215), effects of substitutions of the tyrosine (Y215F, Y215H) were analyzed kinetically, crystallographically and by molecular dynamics simulations. Enzyme variants showed slowed flavin reduction and oxidation by up to 33-fold. Pyruvate release was also decelerated and in Y215F, it was the slowest step overall. A 2.6-A crystal structure of Y215F in complex with pyruvate shows the hydrogen bond between the phenolic hydroxyl and the keto oxygen in pyruvate is replaced with a potentially stronger hydrophobic interaction between the phenylalanine and the methyl group of pyruvate. Residues 200 through 215 or 216 appear to be disordered in two of the eight monomers in the asymmetric unit suggesting that they function as a lid controlling substrate entry and product exit from the active site. Substitutions of Tyr(215) can thus lead to a kinetic bottleneck in product release.
Conformational flexibility related to enzyme activity: evidence for a dynamic active-site gatekeeper function of Tyr(215) in Aerococcus viridans lactate oxidase.,Stoisser T, Brunsteiner M, Wilson DK, Nidetzky B Sci Rep. 2016 Jun 15;6:27892. doi: 10.1038/srep27892. PMID:27302031[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Stoisser T, Rainer D, Leitgeb S, Wilson DK, Nidetzky B. The Ala -to-Gly substitution in Aerococcus viridans L-lactate oxidase revisited: structural consequences at the catalytic site and effect on reactivity with O and other electron acceptors. FEBS J. 2014 Nov 25. doi: 10.1111/febs.13162. PMID:25423902 doi:http://dx.doi.org/10.1111/febs.13162
- ↑ Stoisser T, Klimacek M, Wilson DK, Nidetzky B. Speeding up the product release: a second-sphere contribution from Tyr191 to the reactivity of L-lactate oxidase revealed in crystallographic and kinetic studies of site-directed variants. FEBS J. 2015 Aug 11. doi: 10.1111/febs.13409. PMID:26260739 doi:http://dx.doi.org/10.1111/febs.13409
- ↑ Stoisser T, Brunsteiner M, Wilson DK, Nidetzky B. Conformational flexibility related to enzyme activity: evidence for a dynamic active-site gatekeeper function of Tyr(215) in Aerococcus viridans lactate oxidase. Sci Rep. 2016 Jun 15;6:27892. doi: 10.1038/srep27892. PMID:27302031 doi:http://dx.doi.org/10.1038/srep27892
- ↑ Duncan JD, Wallis JO, Azari MR. Purification and properties of Aerococcus viridans lactate oxidase. Biochem Biophys Res Commun. 1989 Oct 31;164(2):919-26. PMID:2818595 doi:10.1016/0006-291x(89)91546-5
- ↑ Maeda-Yorita K, Aki K, Sagai H, Misaki H, Massey V. L-lactate oxidase and L-lactate monooxygenase: mechanistic variations on a common structural theme. Biochimie. 1995;77(7-8):631-42. PMID:8589073 doi:10.1016/0300-9084(96)88178-8
- ↑ Stoisser T, Brunsteiner M, Wilson DK, Nidetzky B. Conformational flexibility related to enzyme activity: evidence for a dynamic active-site gatekeeper function of Tyr(215) in Aerococcus viridans lactate oxidase. Sci Rep. 2016 Jun 15;6:27892. doi: 10.1038/srep27892. PMID:27302031 doi:http://dx.doi.org/10.1038/srep27892
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