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| | <StructureSection load='2bvh' size='340' side='right'caption='[[2bvh]], [[Resolution|resolution]] 2.90Å' scene=''> | | <StructureSection load='2bvh' size='340' side='right'caption='[[2bvh]], [[Resolution|resolution]] 2.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2bvh]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Atcc_49919 Atcc 49919]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2BVH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2BVH FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2bvh]] 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=2BVH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2BVH FirstGlance]. <br> |
| - | </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> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.9Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2bvf|2bvf]], [[2bvg|2bvg]]</div></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='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/(R)-6-hydroxynicotine_oxidase (R)-6-hydroxynicotine oxidase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.5.3.6 1.5.3.6] </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=2bvh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bvh OCA], [https://pdbe.org/2bvh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2bvh RCSB], [https://www.ebi.ac.uk/pdbsum/2bvh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2bvh ProSAT]</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=2bvh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bvh OCA], [https://pdbe.org/2bvh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2bvh RCSB], [https://www.ebi.ac.uk/pdbsum/2bvh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2bvh ProSAT]</span></td></tr> |
| | </table> | | </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 == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Atcc 49919]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Koetter, J W.A]] | + | [[Category: Paenarthrobacter nicotinovorans]] |
| - | [[Category: Schulz, G E]] | + | [[Category: Koetter JWA]] |
| - | [[Category: Autoflavinylation]] | + | [[Category: Schulz GE]] |
| - | [[Category: Enantiomeric substrate]]
| + | |
| - | [[Category: Flavoenzyme]]
| + | |
| - | [[Category: Nicotine degradation]]
| + | |
| - | [[Category: Oxidase]]
| + | |
| Structural highlights
Function
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).[1] [2] [3] [4] [5]
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
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[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Mauch L, Bichler V, Brandsch R. Site-directed mutagenesis of the FAD-binding histidine of 6-hydroxy-D-nicotine oxidase. Consequences on flavinylation and enzyme activity. FEBS Lett. 1989 Oct 23;257(1):86-8. PMID:2680607 doi:10.1016/0014-5793(89)81792-2
- ↑ Fitzpatrick PF, Dougherty V, Subedi B, Quilantan J, Hinck CS, Lujan AI, Tormos JR. Mechanism of the Flavoprotein d-6-Hydroxynicotine Oxidase: Substrate Specificity, pH and Solvent Isotope Effects, and Roles of Key Active-Site Residues. Biochemistry. 2019 May 28;58(21):2534-2541. PMID:31046245 doi:10.1021/acs.biochem.9b00297
- ↑ Brühmüller M, Möhler H, Decker K. Covalently bound flavin in D-6-hydroxynicotine oxidase from Arthrobacter oxidans. Purification and properties of D-6-hydroxynicotine oxidase. Eur J Biochem. 1972 Aug 18;29(1):143-51. PMID:4628374 doi:10.1111/j.1432-1033.1972.tb01968.x
- ↑ Decker K, Dai VD. Mechanism and specifcity of L Eur J Biochem. 1967 Dec;3(2):132-8. PMID:4965794 doi:10.1111/j.1432-1033.1967.tb19507.x
- ↑ Decker K, Bleeg H. Induction and purification of stereospecific nicotine oxidizing enzymes from Arthrobacter oxidans. Biochim Biophys Acta. 1965 Aug 24;105(2):313-24. PMID:5849820 doi:10.1016/s0926-6593(65)80155-2
- ↑ Koetter JW, Schulz GE. Crystal structure of 6-hydroxy-D-nicotine oxidase from Arthrobacter nicotinovorans. J Mol Biol. 2005 Sep 16;352(2):418-28. PMID:16095622 doi:10.1016/j.jmb.2005.07.041
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