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Redox Specificity of 2-Hydroxyacid-Coupled NAD(+)/NADH Dehydrogenases: A Study Exploiting “Reactive” Arginine as a Reporter of Protein Electrostatics
With “reactive” arginine as a kinetic reporter, 2-hydroxyacid dehydrogenases are assessed in basis of their specialization as NAD(+)-reducing or NADH-oxidizing enzymes. Specifically, M4 and H4 lactate dehydrogenases (LDHs) and cytoplasmic and mitochondrial malate dehydrogenases (MDHs) are compared t...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3877072/ https://www.ncbi.nlm.nih.gov/pubmed/24391777 http://dx.doi.org/10.1371/journal.pone.0083505 |
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author | Gupta, Pooja Jairajpuri, Mohamad Aman Durani, Susheel |
author_facet | Gupta, Pooja Jairajpuri, Mohamad Aman Durani, Susheel |
author_sort | Gupta, Pooja |
collection | PubMed |
description | With “reactive” arginine as a kinetic reporter, 2-hydroxyacid dehydrogenases are assessed in basis of their specialization as NAD(+)-reducing or NADH-oxidizing enzymes. Specifically, M4 and H4 lactate dehydrogenases (LDHs) and cytoplasmic and mitochondrial malate dehydrogenases (MDHs) are compared to assess if their coenzyme specificity may involve electrostatics of cationic or neutral nicotinamide structure as the basis. The enzymes from diverse eukaryote and prokaryote sources thus are assessed in “reactivity” of functionally-critical arginine as a function of salt concentration and pH. Electrostatic calculations were performed on “reactive” arginines and found good correspondence with experiment. The reductive and oxidative LDHs and MDHs are assessed in their count over ionizable residues and in placement details of the residues in their structures as proteins. The variants found to be high or low in ΔpKa of “reactive” arginine are found to be also strong or weak cations that preferentially oxidize NADH (neutral nicotinamide structure) or reduce NAD(+) (cationic nicotinamide structure). The ionized groups of protein structure may thus be important to redox specificity of the enzyme on basis of electrostatic preference for the oxidized (cationic nicotinamide) or reduced (neutral nicotinamide) coenzyme. Detailed comparisons of isozymes establish that the residues contributing in their redox specificity are scrambled in structure of the reductive enzyme. |
format | Online Article Text |
id | pubmed-3877072 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-38770722014-01-03 Redox Specificity of 2-Hydroxyacid-Coupled NAD(+)/NADH Dehydrogenases: A Study Exploiting “Reactive” Arginine as a Reporter of Protein Electrostatics Gupta, Pooja Jairajpuri, Mohamad Aman Durani, Susheel PLoS One Research Article With “reactive” arginine as a kinetic reporter, 2-hydroxyacid dehydrogenases are assessed in basis of their specialization as NAD(+)-reducing or NADH-oxidizing enzymes. Specifically, M4 and H4 lactate dehydrogenases (LDHs) and cytoplasmic and mitochondrial malate dehydrogenases (MDHs) are compared to assess if their coenzyme specificity may involve electrostatics of cationic or neutral nicotinamide structure as the basis. The enzymes from diverse eukaryote and prokaryote sources thus are assessed in “reactivity” of functionally-critical arginine as a function of salt concentration and pH. Electrostatic calculations were performed on “reactive” arginines and found good correspondence with experiment. The reductive and oxidative LDHs and MDHs are assessed in their count over ionizable residues and in placement details of the residues in their structures as proteins. The variants found to be high or low in ΔpKa of “reactive” arginine are found to be also strong or weak cations that preferentially oxidize NADH (neutral nicotinamide structure) or reduce NAD(+) (cationic nicotinamide structure). The ionized groups of protein structure may thus be important to redox specificity of the enzyme on basis of electrostatic preference for the oxidized (cationic nicotinamide) or reduced (neutral nicotinamide) coenzyme. Detailed comparisons of isozymes establish that the residues contributing in their redox specificity are scrambled in structure of the reductive enzyme. Public Library of Science 2013-12-31 /pmc/articles/PMC3877072/ /pubmed/24391777 http://dx.doi.org/10.1371/journal.pone.0083505 Text en © 2013 Gupta et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Gupta, Pooja Jairajpuri, Mohamad Aman Durani, Susheel Redox Specificity of 2-Hydroxyacid-Coupled NAD(+)/NADH Dehydrogenases: A Study Exploiting “Reactive” Arginine as a Reporter of Protein Electrostatics |
title | Redox Specificity of 2-Hydroxyacid-Coupled NAD(+)/NADH Dehydrogenases: A Study Exploiting “Reactive” Arginine as a Reporter of Protein Electrostatics |
title_full | Redox Specificity of 2-Hydroxyacid-Coupled NAD(+)/NADH Dehydrogenases: A Study Exploiting “Reactive” Arginine as a Reporter of Protein Electrostatics |
title_fullStr | Redox Specificity of 2-Hydroxyacid-Coupled NAD(+)/NADH Dehydrogenases: A Study Exploiting “Reactive” Arginine as a Reporter of Protein Electrostatics |
title_full_unstemmed | Redox Specificity of 2-Hydroxyacid-Coupled NAD(+)/NADH Dehydrogenases: A Study Exploiting “Reactive” Arginine as a Reporter of Protein Electrostatics |
title_short | Redox Specificity of 2-Hydroxyacid-Coupled NAD(+)/NADH Dehydrogenases: A Study Exploiting “Reactive” Arginine as a Reporter of Protein Electrostatics |
title_sort | redox specificity of 2-hydroxyacid-coupled nad(+)/nadh dehydrogenases: a study exploiting “reactive” arginine as a reporter of protein electrostatics |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3877072/ https://www.ncbi.nlm.nih.gov/pubmed/24391777 http://dx.doi.org/10.1371/journal.pone.0083505 |
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