Variations within class-a beta-lactamase physiochemical properties reflect evolutionary and environmental patterns, but not antibiotic specificity

Search for this publication on Google Scholar
Jacobs, D. J., Verma, D., & Livesay, D. R. (2013). Variations within class-a beta-lactamase physiochemical properties reflect evolutionary and environmental patterns, but not antibiotic specificity. Plos Computational Biology.
Download PDF

Analytics

60 views ◎
10 downloads ⇓


Description

Faculty, The bacterial enzyme beta-lactamase hydrolyzes the beta-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 beta-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 pK(a) 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.

Details
Title

Variations within class-a beta-lactamase physiochemical properties reflect evolutionary and environmental patterns, but not antibiotic specificity

Author(s)

Jacobs, Donald J.
Verma, Deeptak
Livesay, Dennis R.

UNC Charlotte Affiliate Type

Faculty

Extent

1 online resource

Date Created

2013

Genre

articles

Resource Type

text

Abstract

The bacterial enzyme beta-lactamase hydrolyzes the beta-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 beta-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 pK(a) 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.

Subjects--Topics

Biology
Bacteria

Is Part Of

PLoS computational biology

Language

English

Publisher's Version

doi:10.1371/journal.pcbi.1003155

Permalink

http://hdl.handle.net/20.500.13093/work:969

Rights

This item may be protected by copyright and other related rights. Atkins Library provides access to this item for educational and research purposes only; other uses require the permission of the copyright holder.