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| <StructureSection load='3nk2' size='340' side='right'caption='[[3nk2]], [[Resolution|resolution]] 2.65Å' scene=''> | | <StructureSection load='3nk2' size='340' side='right'caption='[[3nk2]], [[Resolution|resolution]] 2.65Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
- | <table><tr><td colspan='2'>[[3nk2]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Artni Artni]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3NK2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3NK2 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3nk2]] is a 1 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=3NK2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3NK2 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>, <scene name='pdbligand=GP7:(1R)-2-{[(S)-(2-AMINOETHOXY)(HYDROXY)PHOSPHORYL]OXY}-1-[(PENTADECANOYLOXY)METHYL]ETHYL+(12E)-HEXADECA-9,12-DIENOATE'>GP7</scene>, <scene name='pdbligand=LDP:L-DOPAMINE'>LDP</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]] 2.65Å</td></tr> |
- | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3ngc|3ngc]], [[3nh3|3nh3]], [[3nho|3nho]], [[3nk0|3nk0]], [[3nk1|3nk1]], [[3nn0|3nn0]], [[3nn6|3nn6]], [[3k7m|3k7m]], [[3k7q|3k7q]]</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>, <scene name='pdbligand=GP7:(1R)-2-{[(S)-(2-AMINOETHOXY)(HYDROXY)PHOSPHORYL]OXY}-1-[(PENTADECANOYLOXY)METHYL]ETHYL+(12E)-HEXADECA-9,12-DIENOATE'>GP7</scene>, <scene name='pdbligand=LDP:L-DOPAMINE'>LDP</scene></td></tr> |
- | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">6-HLNO ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=29320 ARTNI])</td></tr>
| + | |
- | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/(S)-6-hydroxynicotine_oxidase (S)-6-hydroxynicotine oxidase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.5.3.5 1.5.3.5] </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=3nk2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3nk2 OCA], [https://pdbe.org/3nk2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3nk2 RCSB], [https://www.ebi.ac.uk/pdbsum/3nk2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3nk2 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=3nk2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3nk2 OCA], [https://pdbe.org/3nk2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3nk2 RCSB], [https://www.ebi.ac.uk/pdbsum/3nk2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3nk2 ProSAT]</span></td></tr> |
| </table> | | </table> |
| + | == Function == |
| + | [https://www.uniprot.org/uniprot/HLNO_PAENI HLNO_PAENI] Involved in the degradation of L-nicotine (PubMed:5849820). Catalyzes the oxidation of (S)-6-hydroxynicotine (6-hydroxy-L-nicotine) to 6-hydroxypseudooxynicotine (PubMed:5849820, PubMed:4965794, PubMed:5646150, PubMed:21383134, PubMed:26744768, PubMed:28080034). Oxidation of the pyrrolidine ring of (S)-6-hydroxynicotine leads to the formation of the optically inactive 6-hydroxy-N-methylmyosmine, which hydrolyzes spontaneously to 6-hydroxypseudooxynicotine (PubMed:4965794, PubMed:21383134, PubMed:26744768, PubMed:28080034). Acts with absolute stereospecificity on the L-form of 6-hydroxynicotine (PubMed:4965794). Can also use (S)-6-hydroxynornicotine (PubMed:26744768, PubMed:28080034).<ref>PMID:21383134</ref> <ref>PMID:26744768</ref> <ref>PMID:28080034</ref> <ref>PMID:4965794</ref> <ref>PMID:5646150</ref> <ref>PMID:5849820</ref> |
| <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: Artni]] | |
| [[Category: Large Structures]] | | [[Category: Large Structures]] |
- | [[Category: Bartunik, H D]] | + | [[Category: Paenarthrobacter nicotinovorans]] |
- | [[Category: Kachalova, G S]] | + | [[Category: Bartunik HD]] |
- | [[Category: Enanthiomeric substrate-inhibitor]] | + | [[Category: Kachalova GS]] |
- | [[Category: Flavoenzyme]]
| + | |
- | [[Category: Nicotine degradation]]
| + | |
- | [[Category: Oxidoreductase]]
| + | |
| Structural highlights
Function
HLNO_PAENI Involved in the degradation of L-nicotine (PubMed:5849820). Catalyzes the oxidation of (S)-6-hydroxynicotine (6-hydroxy-L-nicotine) to 6-hydroxypseudooxynicotine (PubMed:5849820, PubMed:4965794, PubMed:5646150, PubMed:21383134, PubMed:26744768, PubMed:28080034). Oxidation of the pyrrolidine ring of (S)-6-hydroxynicotine leads to the formation of the optically inactive 6-hydroxy-N-methylmyosmine, which hydrolyzes spontaneously to 6-hydroxypseudooxynicotine (PubMed:4965794, PubMed:21383134, PubMed:26744768, PubMed:28080034). Acts with absolute stereospecificity on the L-form of 6-hydroxynicotine (PubMed:4965794). Can also use (S)-6-hydroxynornicotine (PubMed:26744768, PubMed:28080034).[1] [2] [3] [4] [5] [6]
Publication Abstract from PubMed
The pathway for oxidative degradation of nicotine in Arthrobacter nicotinovorans includes two genetically and structurally unrelated flavoenzymes, 6-hydroxy-L-nicotine oxidase (6HLNO) and 6-hydroxy-D-nicotine oxidase, which act with absolute stereospecificity on the L- and D-forms, respectively, of 6-hydroxy-nicotine. We solved the crystal structure of 6HLNO at 1.95 A resolution by combined isomorphous/multiple-wavelength anomalous dispersion phasing. The overall structure of each subunit of the 6HLNO homodimer and the folds of the individual domains are closely similar as in eukaryotic monoamine oxidases. Unexpectedly, a diacylglycerophospholipid molecule was found to be non-covalently bound to each protomer of 6HLNO. The fatty acid chains occupy hydrophobic channels that penetrate deep into the interior of the substrate-binding domain of each subunit. The solvent-exposed glycerophosphate moiety is located at the subunit-subunit interface. We further solved the crystal structure of a complex of dithionite-reduced 6HLNO with the natural substrate 6-hydroxy-L-nicotine at 2.05 A resolution. The location of the substrate in a tight cavity suggests that the binding geometry of this unproductive complex may be closely similar as under oxidizing conditions. The observed orientation of the bound substrate relative to the isoalloxazine ring of the flavin adenine dinucleotide cofactor is suitable for hydride-transfer dehydrogenation at the carbon atom that forms the chiral center of the substrate molecule. A comparison of the substrate-binding modes of 6HLNO and 6-hydroxy-D-nicotine oxidase, based on models of complexes with the D-substrate, suggests an explanation for the stereospecificity of both enzymes. The two enzymes are proposed to orient the enantiomeric substrates in mirror symmetry with respect to the plane of the flavin.
Crystal structure analysis of free and substrate-bound 6-hydroxy-L-nicotine oxidase from Arthrobacter nicotinovorans.,Kachalova GS, Bourenkov GP, Mengesdorf T, Schenk S, Maun HR, Burghammer M, Riekel C, Decker K, Bartunik HD J Mol Biol. 2010 Feb 26;396(3):785-99. Epub 2009 Dec 16. PMID:20006620[7]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Kachalova G, Decker K, Holt A, Bartunik HD. Crystallographic snapshots of the complete reaction cycle of nicotine degradation by an amine oxidase of the monoamine oxidase (MAO) family. Proc Natl Acad Sci U S A. 2011 Mar 22;108(12):4800-5. Epub 2011 Mar 7. PMID:21383134 doi:http://dx.doi.org/10.1073/pnas.1016684108
- ↑ Fitzpatrick PF, Chadegani F, Zhang S, Roberts KM, Hinck CS. Mechanism of the Flavoprotein L-Hydroxynicotine Oxidase: Kinetic Mechanism, Substrate Specificity, Reaction Product, and Roles of Active-Site Residues. Biochemistry. 2016 Feb 2;55(4):697-703. PMID:26744768 doi:10.1021/acs.biochem.5b01325
- ↑ Fitzpatrick PF, Chadegani F, Zhang S, Dougherty V. Mechanism of Flavoprotein l-6-Hydroxynicotine Oxidase: pH and Solvent Isotope Effects and Identification of Key Active Site Residues. Biochemistry. 2017 Feb 14;56(6):869-875. PMID:28080034 doi:10.1021/acs.biochem.6b01160
- ↑ 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
- ↑ Dai VD, Decker K, Sund H. Purification and properties of L-6-hydroxynicotine oxidase. Eur J Biochem. 1968 Mar;4(1):95-102. PMID:5646150 doi:10.1111/j.1432-1033.1968.tb00177.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
- ↑ Kachalova GS, Bourenkov GP, Mengesdorf T, Schenk S, Maun HR, Burghammer M, Riekel C, Decker K, Bartunik HD. Crystal structure analysis of free and substrate-bound 6-hydroxy-L-nicotine oxidase from Arthrobacter nicotinovorans. J Mol Biol. 2010 Feb 26;396(3):785-99. Epub 2009 Dec 16. PMID:20006620 doi:10.1016/j.jmb.2009.12.009
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