En shown to be involved in the binding of cell wall

En shown to be involved in the binding of cell wall molecules Gracillin chemical information ofbacteria other than Mycobacterium tuberculosis. These molecules included LPS, LTA and PGN of Gram-negative and Grampositive bacteria [10]. The structure of the ternary complex of CPGRP-S with LPS and SA provides another strong evidence of the recognition potential of CPGRP-S for acting against bacterial infection. The observed forcep-like shape of the cleft formed by two a-helices Aa2 and Ba2 at the A contact provides features similar as that observed in the case of other fatty acid binding proteins [21,22]. On the other hand the cleft at the C contact consists of a specific pocket for the recognition of glycan moieties such as GlcNAc and MurNAc [11]. In a contrast, it was shown in the structures of the complexes of PGRP-S domain of HPGRP-Ia and HPGRP-Ib, that the peptide KS 176 web moiety of PGN was the initial element of recognition by the protein [23,24]. Therefore, the real issue here was whether the specificity pocket at the C contact was 18325633 more suitable for binding to glycan components of PGNs or it suited more to bind to the interlinking peptide Thus it important to understand as to which of the two moieties played a more significant role in the recognition of PGNs by PGRP-S. Since glycan moieties are the conserved chemical entities of bacterial cell wall molecules these might be preferred elements for the recognition. 26001275 This has been shown by several structures of the complexes of CPGRP-S with various PAMPs [9?2,19]. On the other hand, the peptide sequences in PGNs vary considerably and may require a very promiscous peptide recognition site. Also, the peptide components in PGNs interconnect the glycan chains and hence they might not be fully accessible for specific recognition by the protein. In view of these facts and also as observed in the structures of the complexes of CPGRP-S with various PAMPs, the glycan moieties indeed appeared to be more relevant elements for the recognition by CPGRP-S at the C contact. An examination of intermolecular interactions between CPGRP-S and SA and between CPGRP-S and LPS clearly showed that both ligands bound to the protein strongly and independently. As there is no plausible site in CPGRP-S for enzymatic activity, the binding appears to be the only mode ofWide Spectrum Antimicrobial Role of Camel PGRP-Saction. Thus CPGRP-S may sequester bacteria and deprive it of cell-cell communication as well as it may prevent the bacterial contact with the matrix around it. Such an isolation of bacterial cells may eventually cause its death. This process of bacterial killing here appears to be different from that of antibacterial peptides such as defensins that kill bacteria by permeabilization of cell membranes [25], peptidoglycan lytic enzymes which also kill bacteria by causing membrane permeabilization [26]. However, it may have some similarity with the action of antibiotics such as penicillin that may eventually destroy the cell wall of bacteria by inhibiting its synthesis [27]. Thus, the kinetics of bacterial killing by CPGRP-S may be somewhat similar to that of antibiotics and because of this similarity CPGRP-S may also be termed as a protein antibiotic.AcknowledgmentsTPS thanks the Department of Biotechnology (DBT), Ministry of science and Technology, New Delhi for the award of Distinguished Biotechnology research professorship to him. PS thanks Department of Science and Technology for INSPIRE-Faculty award to him.Author ContributionsConceived a.En shown to be involved in the binding of cell wall molecules ofbacteria other than Mycobacterium tuberculosis. These molecules included LPS, LTA and PGN of Gram-negative and Grampositive bacteria [10]. The structure of the ternary complex of CPGRP-S with LPS and SA provides another strong evidence of the recognition potential of CPGRP-S for acting against bacterial infection. The observed forcep-like shape of the cleft formed by two a-helices Aa2 and Ba2 at the A contact provides features similar as that observed in the case of other fatty acid binding proteins [21,22]. On the other hand the cleft at the C contact consists of a specific pocket for the recognition of glycan moieties such as GlcNAc and MurNAc [11]. In a contrast, it was shown in the structures of the complexes of PGRP-S domain of HPGRP-Ia and HPGRP-Ib, that the peptide moiety of PGN was the initial element of recognition by the protein [23,24]. Therefore, the real issue here was whether the specificity pocket at the C contact was 18325633 more suitable for binding to glycan components of PGNs or it suited more to bind to the interlinking peptide Thus it important to understand as to which of the two moieties played a more significant role in the recognition of PGNs by PGRP-S. Since glycan moieties are the conserved chemical entities of bacterial cell wall molecules these might be preferred elements for the recognition. 26001275 This has been shown by several structures of the complexes of CPGRP-S with various PAMPs [9?2,19]. On the other hand, the peptide sequences in PGNs vary considerably and may require a very promiscous peptide recognition site. Also, the peptide components in PGNs interconnect the glycan chains and hence they might not be fully accessible for specific recognition by the protein. In view of these facts and also as observed in the structures of the complexes of CPGRP-S with various PAMPs, the glycan moieties indeed appeared to be more relevant elements for the recognition by CPGRP-S at the C contact. An examination of intermolecular interactions between CPGRP-S and SA and between CPGRP-S and LPS clearly showed that both ligands bound to the protein strongly and independently. As there is no plausible site in CPGRP-S for enzymatic activity, the binding appears to be the only mode ofWide Spectrum Antimicrobial Role of Camel PGRP-Saction. Thus CPGRP-S may sequester bacteria and deprive it of cell-cell communication as well as it may prevent the bacterial contact with the matrix around it. Such an isolation of bacterial cells may eventually cause its death. This process of bacterial killing here appears to be different from that of antibacterial peptides such as defensins that kill bacteria by permeabilization of cell membranes [25], peptidoglycan lytic enzymes which also kill bacteria by causing membrane permeabilization [26]. However, it may have some similarity with the action of antibiotics such as penicillin that may eventually destroy the cell wall of bacteria by inhibiting its synthesis [27]. Thus, the kinetics of bacterial killing by CPGRP-S may be somewhat similar to that of antibiotics and because of this similarity CPGRP-S may also be termed as a protein antibiotic.AcknowledgmentsTPS thanks the Department of Biotechnology (DBT), Ministry of science and Technology, New Delhi for the award of Distinguished Biotechnology research professorship to him. PS thanks Department of Science and Technology for INSPIRE-Faculty award to him.Author ContributionsConceived a.