Next Article in Journal
Measurement Based Quantum Heat Engine with Coupled Working Medium
Previous Article in Journal
Solvability of the p-Adic Analogue of Navier–Stokes Equation via the Wavelet Theory
Previous Article in Special Issue
Coevolutionary Analysis of Protein Subfamilies by Sequence Reweighting
Open AccessArticle

Dynamical Behavior of β-Lactamases and Penicillin- Binding Proteins in Different Functional States and Its Potential Role in Evolution

1
Department of Chemistry, Center for Drug Discovery, Design, and Delivery (CD4), Center for Scientific Computation, Southern Methodist University, Dallas, TX 75275, USA
2
Department of Statistical Science, Southern Methodist University, Dallas, TX 75275, USA
*
Author to whom correspondence should be addressed.
Entropy 2019, 21(11), 1130; https://doi.org/10.3390/e21111130
Received: 15 September 2019 / Revised: 24 October 2019 / Accepted: 15 November 2019 / Published: 19 November 2019
β-Lactamases are enzymes produced by bacteria to hydrolyze β-lactam-based antibiotics, and pose serious threat to public health through related antibiotic resistance. Class A β-lactamases are structurally and functionally related to penicillin-binding proteins (PBPs). Despite the extensive studies of the structures, catalytic mechanisms and dynamics of both β-lactamases and PBPs, the potentially different dynamical behaviors of these proteins in different functional states still remain elusive in general. In this study, four evolutionarily related proteins, including TEM-1 and TOHO-1 as class A β-lactamases, PBP-A and DD-transpeptidase as two PBPs, are subjected to molecular dynamics simulations and various analyses to characterize their dynamical behaviors in different functional states. Penicillin G and its ring opening product serve as common ligands for these four proteins of interest. The dynamic analyses of overall structures, the active sites with penicillin G, and three catalytically important residues commonly shared by all four proteins reveal unexpected cross similarities between Class A β-lactamases and PBPs. These findings shed light on both the hidden relations among dynamical behaviors of these proteins and the functional and evolutionary relations among class A β-lactamases and PBPs. View Full-Text
Keywords: TEM-1; TOHO-1; PBP-A; DD-transpeptidase; conformational changes; catalytic mechanism; evolution TEM-1; TOHO-1; PBP-A; DD-transpeptidase; conformational changes; catalytic mechanism; evolution
Show Figures

Graphical abstract

MDPI and ACS Style

Wang, F.; Zhou, H.; Wang, X.; Tao, P. Dynamical Behavior of β-Lactamases and Penicillin- Binding Proteins in Different Functional States and Its Potential Role in Evolution. Entropy 2019, 21, 1130.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop