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Pathogenic bacteria Neisseria meningitidis cause serious infection i.e. meningitis (infection of the brain) worldwide. Among five pathogenic serogroups, serogroup B causes life threatening illness as there is no effective vaccine available due to its poor immunogenicity. A total of 73 genes in N. meningitidis genome have identified that were proved to be essential for meningococcal disease and were considered as crucial drug targets. We targeted five of those proteins, which are known to involve in amino acid biosynthesis, for homology-based three dimensional structure determinations by MODELLER (v9.19) and evaluated the models by PROSA and PROCHECK programs. Detailed structural analyses of NMB0358, NMB0943, NMB1446, NMB1577 and NMB1814 proteins were carried out during the present research. Based on a high degree of sequence conservation between target and template protein sequences, excellent models were built. The overall three dimensional architectures as well as topologies of all the proteins were quite similar with that of the templates. Active site residues of all the homology models were quite conserved with respect to their respective templates indicating similar catalytic mechanisms in these orthologues. Here, we are reporting, for the first time, detailed three dimensional folds of N. meningitidis pathogenic factors involved in a crucial cellular metabolic pathway. Moreover, the three dimensional structural information of these important drug targets would be utilized in computer-aided drug designing in future. [ABSTRACT FROM AUTHOR]

Stimulation of C-type lectin domain of human dectin-1 receptor by fungal β-glucans causes conformational changes in its cytoplasmic domain which initiates various cellular responses mediated by downstream signaling components. We aimed to build the three-dimensional structures of thecytoplasmic domain as well asC-type lectin domain of human Dectin-1along with their potential ligands through homology modeling.The overall three-dimensional fold of cytoplasmic domain was found to consist of mixed β-sheet whereas,in case of C-type lectin domain antiparallel β- sheets flanked byα-helices were observed. Protein-protein docking strategy was utilized to monitorkey interactions between cytoplasmic domainof dectin-1 receptor and PKCδ, as a prime regulator of Dectin-1 signaling. The interface was observed to have both hydrophilic and hydrophobic amino acid residues maintaining crucial contacts between the two proteins. The given three dimensional structural information can be implicated in structure-based drug designing to discover potential immunomodulators that can interfere with the immune responses and phagocytosis during inflammatory and infectious conditions. [ABSTRACT FROM AUTHOR]