Structural Bioinformatics of Neisseria meningitidis LD-Carboxypeptidase: Implications for Substrate Binding and Specificity

• Published in: Protein Journal Vol. 30; no. 8; pp. 558 - 565
• Main Authors: Rashid, Yasmeen, Kamran Azim, M.
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.12.2011; Springer; Springer Nature B.V
• Subjects: Amino Acid Sequence; Amino acids; Animal Anatomy; Bacteria; Bacterial Proteins - chemistry; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Binding Sites; Biochemistry; Bioinformatics; Bioorganic Chemistry; Carboxypeptidases - chemistry; Carboxypeptidases - genetics; Carboxypeptidases - metabolism; Chemistry; Chemistry and Materials Science; Comparative analysis; Computational Biology; Genomics; Histology; Meningitis; Models, Molecular; Molecular Sequence Data; Morphology; Neisseria meningitidis; Neisseria meningitidis - chemistry; Neisseria meningitidis - enzymology; Neisseria meningitidis - genetics; Organic Chemistry; Proteases; Protein Binding; Protein Structure, Secondary; Proteins; Sequence Alignment; Substrate Specificity; Substrates; LD-carboxypeptidase; Molecular docking; Homology modeling; Hypothetical protein
• ISSN: 1572-3887; 1573-4943; 1875-8355
• DOI: 10.1007/s10930-011-9364-7

Neisseria meningitidis, a gram negative bacterium, is the leading cause of bacterial meningitis and severe sepsis. Neisseria meningitidis genome contains 2,160 predicted coding regions including 1,000 hypothetical genes. Re-annotation of N. meningitidis hypothetical proteins identified nine putative peptidases. Among them, the NMB1620 protein was annotated as LD-carboxypeptidase involved in peptidoglycan recycling. Structural bioinformatics studies of NMB1620 protein using homology modeling and ligand docking were carried out. Structural comparison of substrate binding site of LD-carboxypeptidase was performed based on binding of tetrapeptide substrate ‘ l -alanyl- d -glutamyl-meso-diaminopimelyl- d -alanine’. Inspection of different subsite-forming residues showed changeability in the S1 subsite across different bacterial species. This variability was predicted to provide a structural basis to S1-subsite for accommodating different amino acid residues at P1 position of the tetrapeptide substrate ‘ l -alanyl- d -glutamyl-meso-diaminopimelyl- d -alanine’.