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| | ==STRUCTURE OF THE OCTAMERIC FLAVOENZYME VANILLYL-ALCOHOL OXIDASE IN COMPLEX WITH P-CRESOL== | | ==STRUCTURE OF THE OCTAMERIC FLAVOENZYME VANILLYL-ALCOHOL OXIDASE IN COMPLEX WITH P-CRESOL== |
| - | <StructureSection load='1ahu' size='340' side='right' caption='[[1ahu]], [[Resolution|resolution]] 2.70Å' scene=''> | + | <StructureSection load='1ahu' size='340' side='right'caption='[[1ahu]], [[Resolution|resolution]] 2.70Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1ahu]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Penicillium_simplicissimum Penicillium simplicissimum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1AHU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1AHU FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1ahu]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Penicillium_simplicissimum Penicillium simplicissimum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1AHU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1AHU FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FAA:N5-(4-HYDROXYBENZYL)FLAVIN-ADENINE+DINUCLEOTIDE'>FAA</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]] 2.7Å</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Alcohol_oxidase Alcohol oxidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.3.13 1.1.3.13] </span></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FAA:N5-(4-HYDROXYBENZYL)FLAVIN-ADENINE+DINUCLEOTIDE'>FAA</scene></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=1ahu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ahu OCA], [http://pdbe.org/1ahu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1ahu RCSB], [http://www.ebi.ac.uk/pdbsum/1ahu PDBsum]</span></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=1ahu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ahu OCA], [https://pdbe.org/1ahu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ahu RCSB], [https://www.ebi.ac.uk/pdbsum/1ahu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ahu ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/VAOX_PENSI VAOX_PENSI]] Catalyzes the conversion of vanillin alcohol to vanillin, and also the conversion of a wide range of phenolic compounds bearing side chains of variable size at the para position of the aromatic ring. Crucial for the degradation of the secondary metabolites derived from the degradation of the lignin. Catalyzes besides the oxidation of 4-hydroxybenzyl alcohols, the oxidative deamination of 4-hydroxybenzylamines, the oxidative demethylation of 4-(methoxy-methyl)phenols and the oxidative hydration of 4-allylphenols. Most active with 4-allylphenols. | + | [https://www.uniprot.org/uniprot/VAOX_PENSI VAOX_PENSI] Catalyzes the conversion of vanillin alcohol to vanillin, and also the conversion of a wide range of phenolic compounds bearing side chains of variable size at the para position of the aromatic ring. Crucial for the degradation of the secondary metabolites derived from the degradation of the lignin. Catalyzes besides the oxidation of 4-hydroxybenzyl alcohols, the oxidative deamination of 4-hydroxybenzylamines, the oxidative demethylation of 4-(methoxy-methyl)phenols and the oxidative hydration of 4-allylphenols. Most active with 4-allylphenols. |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ah/1ahu_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ah/1ahu_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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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Alcohol oxidase]] | + | [[Category: Large Structures]] |
| | [[Category: Penicillium simplicissimum]] | | [[Category: Penicillium simplicissimum]] |
| - | [[Category: Mattevi, A]] | + | [[Category: Mattevi A]] |
| - | [[Category: Catalysis]]
| + | |
| - | [[Category: Flavoenzyme]]
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| - | [[Category: Oxidase]]
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| Structural highlights
Function
VAOX_PENSI Catalyzes the conversion of vanillin alcohol to vanillin, and also the conversion of a wide range of phenolic compounds bearing side chains of variable size at the para position of the aromatic ring. Crucial for the degradation of the secondary metabolites derived from the degradation of the lignin. Catalyzes besides the oxidation of 4-hydroxybenzyl alcohols, the oxidative deamination of 4-hydroxybenzylamines, the oxidative demethylation of 4-(methoxy-methyl)phenols and the oxidative hydration of 4-allylphenols. Most active with 4-allylphenols.
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
BACKGROUND: Lignin degradation leads to the formation of a broad spectrum of aromatic molecules that can be used by various fungal micro-organisms as their sole source of carbon. When grown on phenolic compounds, Penicillium simplicissimum induces the strong impression of a flavin-containing vanillyl-alcohol oxidase (VAO). The enzyme catalyses the oxidation of a vast array of substrates, ranging from aromatic amines to 4-alkyphenols. VAO is a member of a novel class of widely distributed oxidoreductases, which use flavin adenine dinucleotide (FAD) as a cofactor covalently bound to the protein. We have carried out the determination of the structure of VAO in order to shed light on the most interesting features of these novel oxidoreductases, such as the functional significance of covalent flavinylation and the mechanism of catalysis. RESULTS: The crystal structure of VAO has been determined in the native state and in complexes with four inhibitors. The enzyme is an octamer with 42 symmetry; the inhibitors bind in a hydrophobic, elongated cavity on the si side of the flavin molecule. Three residues, Tyr108, Tyr503 and Arg504 form an anion-binding subsite, which stabilises the phenolate form of the substrate. The structure of VAO complexed with the inhibitor 4-(1-heptenyl)phenol shows that the catalytic cavity is completely filled by the inhibitor, explaining why alkylphenols bearing aliphatic substituents longer than seven carbon atoms do not bind to the enzyme. CONCLUSIONS: The shape of the active-site cavity controls substrate specificity by providing a 'size exclusion mechanism'. Inside the cavity, the substrate aromatic ring is positioned at an angle of 18 degrees to the flavin ring. This arrangement is ideally suited for a hydride transfer reaction, which is further facilitated by substrate deprotonation. Burying the substrate beneath the protein surface is a recurrent strategy, common to many flavoenzymes that effect substrate oxidation or reduction via hydride transfer.
Crystal structures and inhibitor binding in the octameric flavoenzyme vanillyl-alcohol oxidase: the shape of the active-site cavity controls substrate specificity.,Mattevi A, Fraaije MW, Mozzarelli A, Olivi L, Coda A, van Berkel WJ Structure. 1997 Jul 15;5(7):907-20. PMID:9261083[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Mattevi A, Fraaije MW, Mozzarelli A, Olivi L, Coda A, van Berkel WJ. Crystal structures and inhibitor binding in the octameric flavoenzyme vanillyl-alcohol oxidase: the shape of the active-site cavity controls substrate specificity. Structure. 1997 Jul 15;5(7):907-20. PMID:9261083
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