title: Homology model of surface antigen OmpC from Salmonella typhi and its functional implications.
abstract: Homology based 3D structural model of the immunodominant major surface antigen OmpC from Salmonella typhi, an obligatory human pathogen, was built to understand the possible unique conformational features of its antigenic loops with respect to other immunologically cross reacting porins. The homology model was built based on the known crystal structures of the E. coli porins OmpF and PhoE. Structure based sequence alignment helped to define the structurally conserved regions (SCRs). The SCR regions of OmpC were modelled using the coordinates of corresponding regions from reference proteins. Surface exposed variable regions were modelled based on the sequence similarity and loop search in PDB. Structural refinement based on symmetry restrained energy minimization resulted in an agreeable model for the trimer of OmpC. The resulting model was compared with other porin structures, having b-barrel fold with 16 transmembrane beta-strands, and found that the variable regions are unique in terms of sequence and structure. A ranking of the loops taking into account the antigenic index, the sequence variability, the surface accessibility in the context of the trimer, and the structural variability suggests that loop 4 (151-172), loop 5 (194-218) and loop 6 (237-264) are the best ranked B-cell epitopes. The model provides possible explanations for the functional and unique immunological properties associated with the surface exposed regions and outlines the implications for structure based experimental design.
authors.affiliation: Bioinformatics Centre, Department of Genetic Engineering, School of Biotechnology, Madurai Kamaraj University, India.
authors.forename: A
authors.initials: A
authors.lastname: Arockiasamy
authors.forename: S
authors.initials: S
authors.lastname: Krishnaswamy
mesh_terms: D000595:Amino Acid Sequence; D017124:Conserved Sequence; D004926:Escherichia coli / Q000737:chemistry; D029968:Escherichia coli Proteins; D008956:Models, Chemical; D008958:Models, Molecular; D008969:Molecular Sequence Data; D018272:Porins / Q000737:chemistry*; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D012485:Salmonella typhi / Q000737:chemistry*; D017386:Sequence Homology, Amino Acid; D055672:Static Electricity
chemical_list: D029968:Escherichia coli Proteins; C113724:OmpC protein; C109237:OmpF protein; D018272:Porins; C082922:PhoE protein, E coli