6c4n: Difference between revisions
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==Pseudopaline dehydrogenase (PaODH) - NADP+ bound== | |||
<StructureSection load='6c4n' size='340' side='right'caption='[[6c4n]], [[Resolution|resolution]] 1.95Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6c4n]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_aeruginosa_PAO1 Pseudomonas aeruginosa PAO1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6C4N OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6C4N 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]] 1.95Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <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'>[https://proteopedia.org/fgij/fg.htm?mol=6c4n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6c4n OCA], [https://pdbe.org/6c4n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6c4n RCSB], [https://www.ebi.ac.uk/pdbsum/6c4n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6c4n ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/ODH_PSEAE ODH_PSEAE] Catalyzes the NAD(P)H-dependent reductive condensation of alpha-ketoglutarate to the intermediate formed by the adjacently encoded enzyme PA4836, namely (2S)-2-amino-4-{[(1S)-1-carboxy-2-(1H-imidazol-4-yl)ethyl]amino}butanoate, leading to the production of pseudopaline. This is the last step in the biosynthesis of the metallophore pseudopaline, which is involved in the acquisition of nickel and zinc, and thus enables bacterial growth inside the host, where metal access is limited. Therefore, this enzyme probably contributes to Pseudomonas virulence. Can use neither pyruvate nor oxaloacetate in place of alpha-ketoglutarate (PubMed:29091735, PubMed:29618515). Is two-fold more efficient using NADPH than NADH as the electron donor (PubMed:29618515).<ref>PMID:29091735</ref> <ref>PMID:29618515</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
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. | |||
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> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 6c4n" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Pseudomonas aeruginosa PAO1]] | |||
[[Category: Davis CL]] | |||
[[Category: Lamb AL]] | |||
[[Category: McFarlane JS]] | |||
Latest revision as of 17:55, 4 October 2023
Pseudopaline dehydrogenase (PaODH) - NADP+ boundPseudopaline dehydrogenase (PaODH) - NADP+ bound
Structural highlights
FunctionODH_PSEAE Catalyzes the NAD(P)H-dependent reductive condensation of alpha-ketoglutarate to the intermediate formed by the adjacently encoded enzyme PA4836, namely (2S)-2-amino-4-{[(1S)-1-carboxy-2-(1H-imidazol-4-yl)ethyl]amino}butanoate, leading to the production of pseudopaline. This is the last step in the biosynthesis of the metallophore pseudopaline, which is involved in the acquisition of nickel and zinc, and thus enables bacterial growth inside the host, where metal access is limited. Therefore, this enzyme probably contributes to Pseudomonas virulence. Can use neither pyruvate nor oxaloacetate in place of alpha-ketoglutarate (PubMed:29091735, PubMed:29618515). Is two-fold more efficient using NADPH than NADH as the electron donor (PubMed:29618515).[1] [2] Publication Abstract from PubMedOpine 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. 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[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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