Structural,functional and evolutionary study of in silico three dimensional model of pneumolysin

Streptococcus pneumoniae,a gram-positive cocci shaped bacteria,is the major human pathogen,causing diseases like septic meningitis,otitis media,sinusitis,pneumonia and septicemia. the objective of present study is to gain more knowledge about the function of important domain of the toxin pneumolysin. this study aims to analyze the structural and functional features of pneumolysin and to investigate the residues involved in its pathogenicity.the major virulence factor of this bacterium is a protein,pneumolysin,which is the member of thiol-activated cytolysins. from the three dimensional homology model of the present study,it was found that pneumolysin has four domains,out of which domain 4 is of great importance. it was observed that cys 428 and trp 433 of pneumolysin are of great importance and any mutation in this region highly reduces its cytotoxicity. cys 428 forms hydrophobic contact with ala 373 and trp 436 of the conserved region,while trp 433 is bonded with trp 436 and arg 426 through hydrogen interactions.the particular cysteine residue is present at position 428 and is also sandwiched between β-sheet and trp 436. in pneumolysin,the undecapeptide or the trp-rich loop spans the region (amino acid 427 to 437) and several single amino acid substitutions within this region reduce the cytolytic activity of pneumolysin by up to 99.9% as reported previously. the primary structure of pneumolysin has a total eight tryptophan residues and one cysteine. the undecapeptide region has three tryptophan and one cysteine residue containing 11 amino acid sequence i.e ectglawewwr. cysteine 428 of pneumolysin present in trp-rich motif is responsible to act on cholestrol. pairwise alignment reveals that pneumolysin do not have the n-terminus signal peptide sequence which is present in the template i.e. perfringolysin. this shows that pneumolysin is an intracellular protein and released only upon cell lysis. © 2017,chemical society of pakistan. all rights reserved.