Comparative sequence- and structure-inspired drug design for PilF protein of Neisseria meningitidis.
Serogroup A of Neisseria meningitidis is the organism responsible for causing epidemic diseases in developing countries by a pilus-mediated adhesion to human brain endothelial cells. Type IV pilus assembly protein (PilF) associated with bacterial adhesion, aggregation, invasion, host cell signaling, surface motility, and natural transformation can be considered as a candidate for effective anti-meningococcal drug development. Since the crystal structure of PilF was not available, in the present study, it was modeled after the Z2491 strain (CAM09255.1) using crystal structure of chain A of Vibrio cholerae putative Ntpase EpsE (Protein Data Bank (PDB) ID: 1P9R) and then we based this analysis on sequence comparisons and structural similarity using in silico methods and docking processes, to design a suitable inhibitor molecule. The ligand 3-{(4S)-5-{[(1R)-1-cyclohexylethyl]amino}-4-[(5S)-5-(prop-2-en-1-yl) cyclopent-1-en-1-yl]-1,4-dihydro-7H-pyrrolo[2,3-d] pyrimidin-7-yl}-1,2-dideoxy-b-L-erythro-hex-1-en-3-ulofuranosyl binds to the protein with a binding energy of -8.10 kcal and showed a drug likeness of 0.952 with no predicted health hazard. It can be utilized as a potent inhibitor of N. meningitidis pilus-mediated adhesion to human brain endothelial cells preventing meningeal colonization.
Department of Biology, University of Dayton, Dayton, OH, USA. abhijeetsingh1786@gmail.com.
Abijeet Singh
AS
Mehta
Department of Biology, University of Dayton, Dayton, OH, USA. kirtisnigdha@gmail.com.
Kirti
K
Snigdha
School of Biotechnology, Shri Mata Vaishno Devi University, Katra, J&K, India. sharda.p@smvdu.ac.in.
M Sharada
MS
Potukuchi
Department of Biology, University of Dayton, Dayton, OH, USA. ptsonis1@udayton.edu.
Panagiotis A
PA
Tsonis
D000595:Amino Acid Sequence / Q000235:genetics; D001422:Bacterial Adhesion / Q000235:genetics; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics; D020134:Catalytic Domain / Q000235:genetics; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D015195:Drug Design; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D009345:Neisseria meningitidis / Q000737:chemistry* / Q000235:genetics / Q000472:pathogenicity; D043583:Nucleoside-Triphosphatase / Q000737:chemistry / Q000235:genetics; D011487:Protein Conformation; D014734:Vibrio cholerae / Q000737:chemistry / Q000235:genetics
D001426:Bacterial Proteins; D008024:Ligands; C081816:pilF protein, Neisseria; D043583:Nucleoside-Triphosphatase