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| | <StructureSection load='6c4m' size='340' side='right'caption='[[6c4m]], [[Resolution|resolution]] 1.94Å' scene=''> | | <StructureSection load='6c4m' size='340' side='right'caption='[[6c4m]], [[Resolution|resolution]] 1.94Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6c4m]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_pestis"_(lehmann_and_neumann_1896)_migula_1900 "bacillus pestis" (lehmann and neumann 1896) migula 1900]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6C4M OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6C4M FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6c4m]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Yersinia_pestis Yersinia pestis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6C4M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6C4M FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</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]] 1.94Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">y2835, YP_1249 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=632 "Bacillus pestis" (Lehmann and Neumann 1896) Migula 1900])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</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=6c4m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6c4m OCA], [http://pdbe.org/6c4m PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6c4m RCSB], [http://www.ebi.ac.uk/pdbsum/6c4m PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6c4m 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=6c4m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6c4m OCA], [https://pdbe.org/6c4m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6c4m RCSB], [https://www.ebi.ac.uk/pdbsum/6c4m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6c4m ProSAT]</span></td></tr> |
| | </table> | | </table> |
| - | <div style="background-color:#fffaf0;">
| + | == Function == |
| - | == Publication Abstract from PubMed == | + | [https://www.uniprot.org/uniprot/ODH_YERPE ODH_YERPE] Catalyzes the NADPH-dependent reductive condensation of pyruvate to the intermediate formed by the adjacently encoded enzyme y2836, namely (2S)-2-amino-4-{[(1S)-1-carboxy-2-(1H-imidazol-4-yl)ethyl]amino}butanoate, leading to the production of yersinopine. This is the last step in the biosynthesis of the metallophore yersinopine, which is involved in metal acquisition and thus enables bacterial growth inside the host, where metal access is limited. Therefore, this enzyme probably contributes to Yersinia virulence. Cannot use alpha-ketoglutarate in place of pyruvate, and displays only poor efficiency with oxaloacetate and glyoxylate.<ref>PMID:29618515</ref> |
| - | Opine dehydrogenases (ODH) from the bacterial pathogens Staphylococcus aureus, Pseudomonas aeruginosa, and Yersinia pestis perform the final enzymatic step in the biosynthesis of a new class of opine metallophores, which includes staphylopine, pseudopaline, and yersinopine, respectively. Growing evidence indicates the important role of this pathway in metal acquisition and virulence, including in lung and burn wound infections (P. aeruginosa) and in blood and heart infections (S. aureus). Here, we present a kinetic and structural characterization of these three opine dehydrogenases. A steady-state kinetic analysis revealed that the three enzymes differ in 6;-keto acid and NAD(P)H substrate specificity, and nicotianamine-like substrate stereoselectivity. To explore the structural basis for these differences, we solved five ODH X-ray crystal structures, ranging in resolution from 1.9 A to 2.5 A, with or without NADP(+) bound. Variation in hydrogen bonding with NADPH suggested an explanation for the differential recognition of this substrate by these three enzymes. Our analysis further revealed candidate residues in the active sites required for binding of the 6;-keto acid and nicotianamine-like substrates and for catalysis. This work reports structural and kinetic analyses of enzymes involved in opine metallophore biosynthesis in three important bacterial pathogens of humans.
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| - | Staphylopine, pseudopaline and yersinopine dehydrogenases: a structural and kinetic analysis of a new functional class of opine dehydrogenase.,McFarlane JS, Davis CL, Lamb AL J Biol Chem. 2018 Apr 4. pii: RA118.002007. doi: 10.1074/jbc.RA118.002007. PMID:29618515<ref>PMID:29618515</ref>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div>
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| - | <div class="pdbe-citations 6c4m" style="background-color:#fffaf0;"></div>
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| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Davis, C L]] | + | [[Category: Yersinia pestis]] |
| - | [[Category: Lamb, A L]] | + | [[Category: Davis CL]] |
| - | [[Category: McFarlane, J S]] | + | [[Category: Lamb AL]] |
| - | [[Category: Opine dehydrogenase metallophore siderophore]] | + | [[Category: McFarlane JS]] |
| - | [[Category: Oxidoreductase]]
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| - | [[Category: Yersinopine pseudopaline staphylopine]]
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