β-Lactamase production is the common mechanism of resistance of β-lactam antibiotics. Knowledge of inter-residue interactions in protein structures increases our understanding of protein structure and stability. We have systematically analysed the contribution of C-H···π interactions to the stability of β-lactamases. Most of the interactions are long range and most of the interacting residues are evolutionarily conserved. The occurrence of C-H···π interactions in active sites and metal binding sites is very low in β-lactamases. Hence, C-H···π interactions are important determinants of stability in β-lactamases and they may not play a significant role in specificity. The results from this study provide valuable insights for understanding the stability patterns of β-lactamases and their relation to various other environmental preferences. © 2013 SBIC.

Sudha Ramaiah

Department of Bio-Sciences

School of Bio Sciences and Technology

Vellore Campus

Anand A

Department of Biotechnology

Lavanya P

Vellore Institute of Technology (VIT) is a private university located in&nbsp;Tamil Nadu, India. Founded in 1984, as Vellore Engineering College, the institution offers 20 undergraduate, 34 postgraduate, four integrated and four research programs. It has campuses in Vellore, Amravati, Bhopal and Chennai.

VIT is one of the top ranked private universities in India according to NIRF, THE and QS Rankings.&nbsp;Govt. of India has recognized&nbsp;VIT, Vellore as an&nbsp;Institution of Eminence. This has allowed VIT to take independent quality initiatives and move up in world ranking.

&nbsp;

&nbsp;

VIT University

JBIC Journal of Biological Inorganic Chemistry

Proteins bind with one or more metal ions in their native state to facilitate the biological function of the protein. The study of critical interactions between the biological molecules and metals is an important field of study. In this work, we focus on the functional specificity of residues coordinating with the metals commonly found in β-lactamases, Zn, Mg, Na, Cu, Mn, Ni, Fe, K, and Cd through non-classical interactions. All the residues located in the metal-binding site of β-lactamases are involved in non-classical interactions. The data obtained from this study will be useful to understand the functional role of metal-coordinating residues in the specificity of β-lactamases, thus offering promising strategy to design effective β-lactamase inhibitors. © 2014 Taylor &amp; Francis.

Journal of Coordination Chemistry

Binding site residues in β-lactamases: role in non-classical interactions and metal binding

Studies on intra-protein interactions provide valuable information on protein conformation. The aim of our study is to explore the functional importance of residues participating in N-H⋯π hydrogen bonds in maintaining the conformational stability of β-lactamases. Our results show that most of the residues participating in N-H⋯π hydrogen bond formation are functionally important and play a significant role in stabilizing the structure with more than one stabilizing region. Our findings reveal the importance of N-H⋯π hydrogen bonds in the stability of β-lactamases. These findings may be helpful for medicinal and computational protein chemists working in the area of enzyme mediated antibiotic resistance. © 2013 Elsevier Ltd.

Computers in Biology and Medicine

Computational analysis of N–H⋯π interactions and its impact on the structural stability of β-lactamases

β-lactam group of antibiotics is the most widely used therapeutic molecules for treating bacterial infections. The main mode of bacterial resistance to β-lactams is by β-lactamases. In the present study, we report our results on the role of cation-π interactions in β-lactamases and their environmental preferences. The number of interactions formed by arginine is higher than lysine in the cationic group, while tyrosine is comparatively higher than phenylalanine and tryptophan in the π group. Our results indicate that cation-π interactions might play an important role in the global conformational stability of β-lactamases.

Cell Biochemistry and Biophysics

Cation–π Interactions in β-Lactamases: The Role in Structural Stability

We have investigated the roles played by C-H⋯π interactions in RNA binding proteins. There was an average of 55 C-H⋯π interactions per protein and also there was an average of one significant C-H⋯π interaction for every nine residues in the 59 RNA binding proteins studied. Main-chain to side-chain C-H⋯π interactions is the predominant type of interactions in RNA binding proteins. The donor atom contribution to C-H⋯π interactions was mainly from Phe, Tyr, Trp, Pro, Gly, Lys, His and Ala residues. The acceptor atom contribution to main-chain to side-chain C-H⋯π and side-chain to side-chain C-H⋯π interactions was mainly from Phe and Tyr residues. On the contrary, the acceptor atoms of Trp residues contributed to all the four types of C-H⋯π interactions. Also, Trp contributed both donor and acceptor atoms in main-chain to side-chain, main-chain to side-chain five-member aromatic ring and side-chain to side-chain C-H⋯π interactions. The secondary structure preference analysis of C-H⋯π interacting residues showed that, Arg, Gln, Glu, His, Ile, Leu, Lys, Met, Phe and Tyr preferred to be in helix, while Ala, Asp, Cys, Gly, Trp and Val preferred to be in strand conformation. Long-range C-H⋯π interactions are the predominant type of interactions in RNA binding proteins. More than 50% of C-H⋯π interacting residues had a higher conservation score. Significant percentage of C-H⋯π interacting residues had one or more stabilization centers. Seven percent of the theoretically predicted stabilizing residues were also involved in C-H⋯π interactions and hence these residues may also contribute additional stability to RNA binding proteins. © 2007 Elsevier B.V. All rights reserved.

International Journal of Biological Macromolecules

Investigations on C–H⋯π interactions in RNA binding proteins

The environmental preference for the occurrence of noncanonical hydrogen bonding and cation-π interactions, in a data set containing 71 nonredundant (α/β)8 barrel proteins, with respect to amine acid type, secondary structure, solvent accessibility, and stabilizing residues has been performed. Our analysis reveals some important findings, which include (a) higher contribution of weak interactions mediated by main-chain atoms irrespective of the amino acids involved; (b) domination of the aromatic amino acids among interactions involving side-chain atoms; (c) involvement of strands as the principal secondary structural unit, accommodating cross strand ion pair interaction and clustering of aromatic amino acid residues; (d) significant contribution to weak interactions occur in the solvent exposed areas of the protein; (e) majority of the interactions involve long-range contacts; (f) the preference of Arg is higher than Lys to form cation-π interaction; and (g) probability of theoretically predicted stabilizing amino acid residues involved in weak interaction is higher for polar amino acids such as Trp, Glu, and Gln. On the whole, the present study reveals that the weak interactions contribute to the global stability of (α/β)8 TIM-barrel proteins in an environment-specific manner, which can possibly be exploited for protein engineering applications. © 2006 Wiley-Liss, Inc.

Journal	Data powered by TypesetJBIC Journal of Biological Inorganic Chemistry
Publisher	Data powered by TypesetSpringer Science and Business Media LLC
ISSN	0949-8257
Open Access	0