β-Lactamases produced by pathogenic bacteria cleave β-lactam antibiotics and render them ineffective. Understanding the principles that govern the structural stability of β-lactamases requires elucidation of the nature of the interactions that are involved in stabilization. In the present study, we systematically analyze the influence of CH.O interactions on determining the specificity and stability of β-lactamases in relation to environmental preferences. It is interesting to note that all the residues located in the active site of β-lactamases are involved in CH.O interactions. A significant percentage of CH.O interactions have a higher conservation score and short-range interactions are the predominant type of interactions in β-lactamases. These results will be useful in understanding the stability patterns of β-lactamases. © 2013 Springer Science+Business Media Dordrecht.

Sudha Ramaiah

Department of Bio-Sciences

School of Bio Sciences and Technology

Vellore Campus

Anand A

Department of Biotechnology

Lavanya P

Fulltext

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.

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VIT University

Journal of Biological Physics

Penicillin binding proteins are recognized as important antibacterial targets because of their crucial role in the cell wall synthesis of bacteria. Alteration in the binding site of penicillin binding proteins is one of the major problems for beta lactam antibiotics to exert its effect. In the present study the influence of CH...O interactions in the conformational stability of penicillin binding proteins were analyzed in both Gram positive and Gram negative bacteria. CH...O interactions constitute about 20 to 25% of total hydrogen bonds and act as an important driving force in ligand selectivity. From our analysis we observed a total of 13,398 CH...O interactions in Gram positive bacteria and 10,855 CH...O interactions in Gram negative bacteria. It was interesting to observe that CH...O interactions were higher in Gram positive bacteria than in Gram negative bacteria, which augurs well for the discrepancy in cell wall of the bacteria. CH...O interactions are classified into four types depending on the interaction of acceptor residues with the back bone or side chain of CH groups. From our results we observed that major contribution to penicillin binding proteins was observed from side chain atoms of donor residues and back bone atoms of acceptor residues [SM CH...O] in both Gram positive and Gram negative bacteria. Conformational preference of Gram positive bacteria indicated that amino acids lacking side chain and the cyclized amino acids preferred to be in turn regions, whereas aromatic amino acids dominated in Gram negative bacteria. Our analysis gives detailed information about the principles involved in the conformational stability of penicillin binding proteins and the results will be useful for researchers exploring penicillin binding proteins. © 2015 Elsevier Ltd.

Computers in Biology and Medicine

Investigations on the role of CH…O interactions and its impact on stability and specificity of penicillin binding proteins

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

Glycoproteins are an important class of proteins that play a significant role in many cellular events. In the present study, we analyze the influence of C-H⋯O interactions in relation to other environmental preferences in glycoproteins. CH⋯O interactions are now accepted as a genuine hydrogen bond. Main chain-main chain interactions are predominant. Proline residues stabilize strands by C-H⋯O interactions in glycoproteins. Majority of the C-H⋯O interacting residues were conserved and had one or more stabilization centers. CH⋯O interactions might be responsible for the global conformational stability, since long-range CH⋯O contacts were predominant. The results presented in this study might be useful for structural stability studies in glycoproteins. © 2009 Humana Press.

Applied Biochemistry and Biotechnology

Exploring the C–H…O Interactions in Glycoproteins

We have investigated the roles played by C{single bond}H⋯O{double bond, long}C interactions in RNA binding proteins. There was an average of 78 C{single bond}H⋯O{double bond, long}C interactions per protein and also there was an average of one significant C{single bond}H⋯O{double bond, long}C interaction for every 6 residues in the 59 RNA binding proteins studied. Main chain-Main chain (MM) C{single bond}H⋯O{double bond, long}C interactions are the predominant type of interactions in RNA binding proteins. The donor atom contribution to C{single bond}H⋯O{double bond, long}C interactions was mainly from aliphatic residues. The acceptor atom contribution for MM C{single bond}H⋯O{double bond, long}C interactions was mainly from Val, Phe, Leu, Ile, Arg and Ala. The secondary structure preference analysis of C{single bond}H⋯O{double bond, long}C interacting residues showed that, Arg, Gln, Glu and Tyr preferred to be in helix, while Ala, Asp, Cys, Gly, Ile, Leu, Lys, Met, Phe, Trp and Val preferred to be in strand conformation. Most of the C{single bond}H⋯O{double bond, long}C interacting polar amino acid residues were solvent exposed while, majority of the C{single bond}H⋯O{double bond, long}C interacting non polar residues were excluded from the solvent. Long and medium-range C{single bond}H⋯O{double bond, long}C interactions are the predominant type of interactions in RNA binding proteins. More than 50% of C{single bond}H⋯O{double bond, long}C interacting residues had a higher conservation score. Significant percentage of C{single bond}H⋯O{double bond, long}C interacting residues had one or more stabilization centers. Sixty-six percent of the theoretically predicted stabilizing residues were also involved in C{single bond}H⋯O{double bond, long}C interactions and hence these residues may also contribute additional stability to RNA binding proteins. © 2007 Elsevier Ireland Ltd. All rights reserved.

Biosystems

Investigations on unconventional hydrogen bonds in RNA binding proteins: The role of CH⋯OC interactions

International Journal of Molecular Sciences

Comparison of Different Ranking Methods in Protein-Ligand Binding Site Prediction

Bioinformatics

Ligand-binding site prediction using ligand-interacting and binding site-enriched protein triangles

Journal of Chemical Information and Modeling

LigPlot+: Multiple Ligand–Protein Interaction Diagrams for Drug Discovery

Influence of C-H...O interactions on the structural stability of β-lactamases

Journal	Data powered by TypesetJournal of Biological Physics
Publisher	Data powered by TypesetSpringer Science and Business Media LLC
ISSN	0092-0606
Open Access	Yes