2bvg
From Proteopedia
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| - | [[Image:2bvg.gif|left|200px]] | ||
| - | + | ==Crystal structure of 6-hydoxy-D-nicotine oxidase from Arthrobacter nicotinovorans. Crystal Form 1 (P21)== | |
| - | + | <StructureSection load='2bvg' size='340' side='right'caption='[[2bvg]], [[Resolution|resolution]] 3.18Å' scene=''> | |
| - | + | == Structural highlights == | |
| - | + | <table><tr><td colspan='2'>[[2bvg]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Paenarthrobacter_nicotinovorans Paenarthrobacter nicotinovorans]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2BVG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2BVG FirstGlance]. <br> | |
| - | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.18Å</td></tr> | |
| - | --> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</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=2bvg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bvg OCA], [https://pdbe.org/2bvg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2bvg RCSB], [https://www.ebi.ac.uk/pdbsum/2bvg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2bvg ProSAT]</span></td></tr> | |
| - | + | </table> | |
| - | + | == Function == | |
| - | + | [https://www.uniprot.org/uniprot/HDNO_PAENI HDNO_PAENI] Involved in the degradation of D-nicotine (PubMed:5849820, PubMed:4628374). Catalyzes the oxidation of (R)-6-hydroxynicotine (6-hydroxy-D-nicotine) to 6-hydroxypseudooxynicotine (PubMed:5849820, PubMed:4965794, PubMed:4628374, PubMed:2680607, PubMed:31046245). Oxidation of the pyrrolidine ring of (R)-6-hydroxynicotine leads to the formation of the optically inactive 6-hydroxy-N-methylmyosmine, which hydrolyzes spontaneously to 6-hydroxypseudooxynicotine (PubMed:4965794, PubMed:4628374, PubMed:31046245). Acts with absolute stereospecificity on the D-form of 6-hydroxynicotine (PubMed:4965794, PubMed:4628374). Shows lower activity with (R)-6-hydroxynornicotine, and weak activity with (R)-4-(1-methylpyrrolidine-2-yl)phenol, (R)-6-chloronicotine and (R)-nicotine (PubMed:31046245).<ref>PMID:2680607</ref> <ref>PMID:31046245</ref> <ref>PMID:4628374</ref> <ref>PMID:4965794</ref> <ref>PMID:5849820</ref> | |
| - | + | == Evolutionary Conservation == | |
| - | == | + | [[Image:Consurf_key_small.gif|200px|right]] |
| + | Check<jmol> | ||
| + | <jmolCheckbox> | ||
| + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/bv/2bvg_consurf.spt"</scriptWhenChecked> | ||
| + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
| + | <text>to colour the structure by Evolutionary Conservation</text> | ||
| + | </jmolCheckbox> | ||
| + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2bvg ConSurf]. | ||
| + | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
The crystal structure of 6-hydroxy-d-nicotine oxidase (EC 1.5.3.6) was solved by X-ray diffraction analysis in three crystal forms at resolutions up to 1.9 A. The enzyme is monomeric in solution and also in the mother liquor but formed disulfide-dimers in all crystals. It belongs to the p-cresol methylhydroxylase-vanillyl-alcohol oxidase family and contains an FAD covalently bound to the polypeptide. The covalent bond of this enzyme was the first for which a purely autocatalytic formation had been shown. In contrast to previous reports, the bond does not involve N(epsilon2) (N3) of His72 but the N(delta1) (N1) atom. The geometry of this reaction is proposed and the autoflavinylation is discussed in the light of homologous structures. The enzyme is specific for 6-hydroxy-D-nicotine and is inhibited by the L-enantiomer. This observation was verified by modeling enzyme-substrate and enzyme-inhibitor complexes, which also showed the geometry of the catalyzed reaction. The binding models indicated that the deprotonation of the substrate rather than the hydride transfer is the specificity-determining step. The functionally closely related 6-hydroxy-L-nicotine oxidase processing the L-enantiomer is sequence-related to the greater glutathione reductase family with quite a different chainfold. A model of this "sister enzyme" derived from known homologous structures suggests that the reported L-substrate specificity and D-enantiomer inhibition are also determined by the location of the deprotonating base. | The crystal structure of 6-hydroxy-d-nicotine oxidase (EC 1.5.3.6) was solved by X-ray diffraction analysis in three crystal forms at resolutions up to 1.9 A. The enzyme is monomeric in solution and also in the mother liquor but formed disulfide-dimers in all crystals. It belongs to the p-cresol methylhydroxylase-vanillyl-alcohol oxidase family and contains an FAD covalently bound to the polypeptide. The covalent bond of this enzyme was the first for which a purely autocatalytic formation had been shown. In contrast to previous reports, the bond does not involve N(epsilon2) (N3) of His72 but the N(delta1) (N1) atom. The geometry of this reaction is proposed and the autoflavinylation is discussed in the light of homologous structures. The enzyme is specific for 6-hydroxy-D-nicotine and is inhibited by the L-enantiomer. This observation was verified by modeling enzyme-substrate and enzyme-inhibitor complexes, which also showed the geometry of the catalyzed reaction. The binding models indicated that the deprotonation of the substrate rather than the hydride transfer is the specificity-determining step. The functionally closely related 6-hydroxy-L-nicotine oxidase processing the L-enantiomer is sequence-related to the greater glutathione reductase family with quite a different chainfold. A model of this "sister enzyme" derived from known homologous structures suggests that the reported L-substrate specificity and D-enantiomer inhibition are also determined by the location of the deprotonating base. | ||
| - | + | Crystal structure of 6-hydroxy-D-nicotine oxidase from Arthrobacter nicotinovorans.,Koetter JW, Schulz GE J Mol Biol. 2005 Sep 16;352(2):418-28. PMID:16095622<ref>PMID:16095622</ref> | |
| - | + | ||
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | <div class="pdbe-citations 2bvg" style="background-color:#fffaf0;"></div> | |
| - | + | == References == | |
| - | + | <references/> | |
| - | + | __TOC__ | |
| - | + | </StructureSection> | |
| - | [[Category: | + | [[Category: Large Structures]] |
| - | [[Category: | + | [[Category: Paenarthrobacter nicotinovorans]] |
| - | [[Category: | + | [[Category: Koetter JWA]] |
| - | [[Category: | + | [[Category: Schulz GE]] |
| - | + | ||
Current revision
Crystal structure of 6-hydoxy-D-nicotine oxidase from Arthrobacter nicotinovorans. Crystal Form 1 (P21)
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