Variations within class-A β-lactamase physiochemical properties reflect evolutionary and environmental patterns, but not antibiotic specificity.

The bacterial enzyme β-lactamase hydrolyzes the β-lactam ring of penicillin and chemically related antibiotics, rendering them ineffective. Due to rampant antibiotic overuse, the enzyme is evolving new resistance activities at an alarming rate. Related, the enzyme's global physiochemical proper...

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Autores principales:	Deeptak Verma, Donald J Jacobs, Dennis R Livesay
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/920d440414d440ddaf50f08ac11281d2
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spelling	oai:doaj.org-article:920d440414d440ddaf50f08ac11281d22021-11-18T05:51:58ZVariations within class-A β-lactamase physiochemical properties reflect evolutionary and environmental patterns, but not antibiotic specificity.1553-734X1553-735810.1371/journal.pcbi.1003155https://doaj.org/article/920d440414d440ddaf50f08ac11281d22013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23874193/pdf/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358The bacterial enzyme β-lactamase hydrolyzes the β-lactam ring of penicillin and chemically related antibiotics, rendering them ineffective. Due to rampant antibiotic overuse, the enzyme is evolving new resistance activities at an alarming rate. Related, the enzyme's global physiochemical properties exhibit various amounts of conservation and variability across the family. To that end, we characterize the extent of property conservation within twelve different class-A β-lactamases, and conclusively establish that the systematic variations therein parallel their evolutionary history. Large and systematic differences within electrostatic potential maps and pairwise residue-to-residue couplings are observed across the protein, which robustly reflect phylogenetic outgroups. Other properties are more conserved (such as residue pKa values, electrostatic networks, and backbone flexibility), yet they also have systematic variations that parallel the phylogeny in a statistically significant way. Similarly, the above properties also parallel the environmental condition of the bacteria they are from in a statistically significant way. However, it is interesting and surprising that the only one of the global properties (protein charge) parallels the functional specificity patterns; meaning antibiotic resistance activities are not significantly constraining the global physiochemical properties. Rather, extended spectrum activities can emerge from the background of nearly any set of electrostatic and dynamic properties.Deeptak VermaDonald J JacobsDennis R LivesayPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 9, Iss 7, p e1003155 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Deeptak Verma Donald J Jacobs Dennis R Livesay Variations within class-A β-lactamase physiochemical properties reflect evolutionary and environmental patterns, but not antibiotic specificity.
description	The bacterial enzyme β-lactamase hydrolyzes the β-lactam ring of penicillin and chemically related antibiotics, rendering them ineffective. Due to rampant antibiotic overuse, the enzyme is evolving new resistance activities at an alarming rate. Related, the enzyme's global physiochemical properties exhibit various amounts of conservation and variability across the family. To that end, we characterize the extent of property conservation within twelve different class-A β-lactamases, and conclusively establish that the systematic variations therein parallel their evolutionary history. Large and systematic differences within electrostatic potential maps and pairwise residue-to-residue couplings are observed across the protein, which robustly reflect phylogenetic outgroups. Other properties are more conserved (such as residue pKa values, electrostatic networks, and backbone flexibility), yet they also have systematic variations that parallel the phylogeny in a statistically significant way. Similarly, the above properties also parallel the environmental condition of the bacteria they are from in a statistically significant way. However, it is interesting and surprising that the only one of the global properties (protein charge) parallels the functional specificity patterns; meaning antibiotic resistance activities are not significantly constraining the global physiochemical properties. Rather, extended spectrum activities can emerge from the background of nearly any set of electrostatic and dynamic properties.
format	article
author	Deeptak Verma Donald J Jacobs Dennis R Livesay
author_facet	Deeptak Verma Donald J Jacobs Dennis R Livesay
author_sort	Deeptak Verma
title	Variations within class-A β-lactamase physiochemical properties reflect evolutionary and environmental patterns, but not antibiotic specificity.
title_short	Variations within class-A β-lactamase physiochemical properties reflect evolutionary and environmental patterns, but not antibiotic specificity.
title_full	Variations within class-A β-lactamase physiochemical properties reflect evolutionary and environmental patterns, but not antibiotic specificity.
title_fullStr	Variations within class-A β-lactamase physiochemical properties reflect evolutionary and environmental patterns, but not antibiotic specificity.
title_full_unstemmed	Variations within class-A β-lactamase physiochemical properties reflect evolutionary and environmental patterns, but not antibiotic specificity.
title_sort	variations within class-a β-lactamase physiochemical properties reflect evolutionary and environmental patterns, but not antibiotic specificity.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/920d440414d440ddaf50f08ac11281d2
work_keys_str_mv	AT deeptakverma variationswithinclassablactamasephysiochemicalpropertiesreflectevolutionaryandenvironmentalpatternsbutnotantibioticspecificity AT donaldjjacobs variationswithinclassablactamasephysiochemicalpropertiesreflectevolutionaryandenvironmentalpatternsbutnotantibioticspecificity AT dennisrlivesay variationswithinclassablactamasephysiochemicalpropertiesreflectevolutionaryandenvironmentalpatternsbutnotantibioticspecificity
_version_	1718424743921582080

Variations within class-A β-lactamase physiochemical properties reflect evolutionary and environmental patterns, but not antibiotic specificity.

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