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.

Jayaraman G

Department of Biotechnology

School of Bio Sciences and Technology

Vellore Campus

Chakkaravarthi S

Babu M.M

Gromiha M.M

Sethumadhavan R.

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

Proteins: Structure, Function, and Bioinformatics

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

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.

JBIC Journal of Biological Inorganic Chemistry

Non-canonical H-bonds in β-lactamases: importance of C–H···π interactions

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

We have analyzed and compared the influence of cation-π interactions in glycoproteins (GPs), lipid-binding proteins (LBPs) and RNA-binding proteins (RBPs) in this study. We observed that all the proteins included in the study had profound cation-π interactions. There is an average of one energetically significant cation-π interaction for every 71 residues in GPs, for every 58 residues in LBPs and for every 64 residues in RBPs. Long-range contacts are predominant in all the three types of proteins studied. The pair-wise cation-π interaction energy between the positively charged and aromatic residues shows that Arg-Trp pair energy was the strongest among all six possible pairs in all the three types of proteins studied. There were considerable differences in the preference of cation-π interacting residues to different secondary structure elements and ASA and these might contribute to differences in biochemical functions of GPs, LBPs and RBPs. It was interesting to note that all the five residues involved in cation-π interactions were found to have stabilization centers in GPs, LBPs and RBPs. Majority of the cation-π interacting residues investigated in the present study had a conservation score of ≥6, the cutoff value used to identify the stabilizing residues. A small percentage of cation-π interacting residues were also present as stabilizing residues. The cation-π interaction-forming residues play an important role in the structural stability of in GPs, LBPs and RBPs. The results obtained in this study will be helpful in further understanding the stability, specificity and differences in the biochemical functions of GPs, LBPs and RBPs. © 2007 Elsevier Ltd. All rights reserved.

Journal of Theoretical Biology

Exploring the role of cation–π interactions in glycoproteins lipid-binding proteins and RNA-binding proteins

The energy contribution due to cation-π interactions has been computed for 37 RNA binding proteins. The contribution of these cation-π interacting residues in sequential separation, secondary structure involvement, solvent accessibility, and stabilization centers has been evaluated. Sequential separation of the cation-π involving residues show that, long range contacts predominates in all the proteins studied. Lys and Arg prefers to be in helical structures. Of the cation-π interacting residues, Arg and Lys were in the exposed regions and the aromatic residues (Phe, Tyr and Trp) were in the buried and partially buried regions in the protein structures. Stabilization centers for these proteins showed that all the five residues found in cation-π interactions are important in locating one or more of such centers. On the whole, the results presented in this work will be very useful for further investigations on the specificity and selectivity of RNA binding proteins and also for their structural studies. © 2006 Elsevier B.V. All rights reserved.

Influence of cation-π interactions on RNA-binding proteins

Protein Science

The geometry and efficacy of cation-π interactions in a diagonal position of a designed β-hairpin

Chemical Reviews

Catalytic Versatility, Stability, and Evolution of the (βα)8-Barrel Enzyme Fold

Structural analysis of residues involving cation-π interactions in different folding types of membrane proteins

BMC Structural Biology

10.1186/1472-6807-5-4

Progress in Biophysics and Molecular Biology

Inter-residue interactions in protein folding and stability

Exploring the environmental preference of weak interactions in (α/β)8 barrel proteins

Journal	Data powered by TypesetProteins: Structure, Function, and Bioinformatics
Publisher	Data powered by TypesetWiley
ISSN	0887-3585
Open Access	Yes