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| | <StructureSection load='4zcc' size='340' side='right'caption='[[4zcc]], [[Resolution|resolution]] 2.00Å' scene=''> | | <StructureSection load='4zcc' size='340' side='right'caption='[[4zcc]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4zcc]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Pse14 Pse14]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ZCC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ZCC FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4zcc]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_savastanoi_pv._phaseolicola_1448A Pseudomonas savastanoi pv. phaseolicola 1448A]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ZCC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ZCC FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=NAI:1,4-DIHYDRONICOTINAMIDE+ADENINE+DINUCLEOTIDE'>NAI</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]] 1.997Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PSPPH_1014 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=264730 PSE14])</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=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=NAI:1,4-DIHYDRONICOTINAMIDE+ADENINE+DINUCLEOTIDE'>NAI</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Renalase Renalase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.6.3.5 1.6.3.5] </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=4zcc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zcc OCA], [https://pdbe.org/4zcc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4zcc RCSB], [https://www.ebi.ac.uk/pdbsum/4zcc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4zcc ProSAT]</span></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=4zcc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zcc OCA], [http://pdbe.org/4zcc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4zcc RCSB], [http://www.ebi.ac.uk/pdbsum/4zcc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4zcc ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/RNLS_PSE14 RNLS_PSE14] Catalyzes the oxidation of the 1,2-dihydro- and 1,6-dihydro- isomeric forms of beta-NAD(P) back to beta-NAD(P)+. Has a preference for 1,2-dihydro-beta-NAD as substrate. May serve to protect primary metabolism dehydrogenases from inhibition by the 1,2-dihydro- and 1,6-dihydro-beta-NAD(P) isomers.<ref>PMID:26016690</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Pse14]] | + | [[Category: Pseudomonas savastanoi pv. phaseolicola 1448A]] |
| - | [[Category: Renalase]]
| + | [[Category: Moran GR]] |
| - | [[Category: Moran, G R]] | + | [[Category: Roman JV]] |
| - | [[Category: Roman, J V]] | + | [[Category: Silvaggi NR]] |
| - | [[Category: Silvaggi, N R]] | + | |
| - | [[Category: Flavoenzyme]]
| + | |
| - | [[Category: Oxidase]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| Structural highlights
Function
RNLS_PSE14 Catalyzes the oxidation of the 1,2-dihydro- and 1,6-dihydro- isomeric forms of beta-NAD(P) back to beta-NAD(P)+. Has a preference for 1,2-dihydro-beta-NAD as substrate. May serve to protect primary metabolism dehydrogenases from inhibition by the 1,2-dihydro- and 1,6-dihydro-beta-NAD(P) isomers.[1]
Publication Abstract from PubMed
Despite a lack of convincing in vitro evidence and a number of sound refutations, it is widely accepted that renalase is an enzyme unique to animals that catalyzes the oxidative degradation of catecholamines in blood in order to lower vascular tone. Very recently, we identified isomers of beta-NAD(P)H as substrates for renalase (Beaupre, B. A. et al. (2015) Biochemistry, 54, 795-806). These molecules carry the hydride equivalent on the 2 or 6 position of the nicotinamide base and presumably arise in nonspecific redox reactions of nicotinamide dinucleotides. Renalase serves to rapidly oxidize these isomers to form beta-NAD(P)(+) and then pass the electrons to dioxygen, forming H2O2. We have also shown that these substrate molecules are highly inhibitory to dehydrogenase enzymes and thus have proposed an intracellular metabolic role for this enzyme. Here, we identify a renalase from an organism without a circulatory system. This bacterial form of renalase has the same substrate specificity profile as that of human renalase but, in terms of binding constant (Kd), shows a marked preference for substrates derived from beta-NAD(+). 2-dihydroNAD(P) substrates reduce the enzyme with rate constants (kred) that greatly exceed those for 6-dihydroNAD(P) substrates. Taken together, kred/Kd values indicate a minimum 20-fold preference for 2DHNAD. We also offer the first structures of a renalase in complex with catalytically relevant ligands beta-NAD(+) and beta-NADH (the latter being an analogue of the substrate(s)). These structures show potential electrostatic repulsion interactions with the product and a unique binding orientation for the substrate nicotinamide base that is consistent with the identified activity.
Bacterial Renalase: Structure and Kinetics of an Enzyme with 2- and 6-Dihydro-beta-NAD(P) Oxidase Activity from Pseudomonas phaseolicola.,Hoag MR, Roman J, Beaupre BA, Silvaggi NR, Moran GR Biochemistry. 2015 Jun 23;54(24):3791-802. doi: 10.1021/acs.biochem.5b00451. Epub, 2015 Jun 9. PMID:26016690[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Hoag MR, Roman J, Beaupre BA, Silvaggi NR, Moran GR. Bacterial Renalase: Structure and Kinetics of an Enzyme with 2- and 6-Dihydro-beta-NAD(P) Oxidase Activity from Pseudomonas phaseolicola. Biochemistry. 2015 Jun 23;54(24):3791-802. doi: 10.1021/acs.biochem.5b00451. Epub, 2015 Jun 9. PMID:26016690 doi:http://dx.doi.org/10.1021/acs.biochem.5b00451
- ↑ Hoag MR, Roman J, Beaupre BA, Silvaggi NR, Moran GR. Bacterial Renalase: Structure and Kinetics of an Enzyme with 2- and 6-Dihydro-beta-NAD(P) Oxidase Activity from Pseudomonas phaseolicola. Biochemistry. 2015 Jun 23;54(24):3791-802. doi: 10.1021/acs.biochem.5b00451. Epub, 2015 Jun 9. PMID:26016690 doi:http://dx.doi.org/10.1021/acs.biochem.5b00451
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