Computational Analysis and Binding Site Identification of Type III Secretion System ATPase from Pseudomonas aeruginosa.
In many gram-negative bacteria, the type III secretion system (T3SS), as a virulence factor, is an attractive target for developing novel antibacterial. Regarding this, in our study, we aimed to identify the putative drug target for Pseudomonas aeruginosa, considering ATPase enzyme involved in the type III secretion system. Selective protein sequence of P. aeruginosa involved in the T3SS was retrieved from NCBI databases, and its homologues were subjected to phylogenetic analysis. Its association in T3SS was analyzed via STRING, and the 3D structure was determined by means of homology modeling followed by intensive optimization and validation. The binding site was predicted by 3DLigandSite and examined through molecular docking simulation by Autodock Vina with salicylidene acylhydrazide class of virulence-blocking compounds. PROCHECK analysis showed that 96.7 % of the residues were in the most favored regions, 1.9 % were in the additional allowed region, and 1.4 % were in the generously allowed region of the Ramachandran plot. The refined model yielded ERRAT scores of 88.124 and Verify3D value of 0.2, which indicates that the environmental profile of the model is good. The best binding affinity was observed by ME0055 compound, and ALA160, ALA161, GlY162, GLY163, GLY164, GLY165, SER166, THR167, TYR338, and PRO339 residues were found to be having complementary in the ligand-binding site. However, these findings should be further confirmed by wet lab studies for design a targeted therapeutic agent.
Department of Pharmacy, BGC Trust University Bangladesh, Chittagong, 4000, Bangladesh.
Raju
R
Dash
Drugs and Toxins Research Division, Bangladesh Council of Scientific and Industrial Research (BCSIR), Chittagong, 4220, Bangladesh.
S M Zahid
SM
Hosen
Department of Pharmacy, BGC Trust University Bangladesh, Chittagong, 4000, Bangladesh.
Tasniha
T
Sultana
Department of Pharmaceutical Sciences, North South University, Dhaka, 1229, Bangladesh.
Md
M
Junaid
Department of Pharmacy, BGC Trust University Bangladesh, Chittagong, 4000, Bangladesh.
Mohuya
M
Majumder
Department of Pharmacy, BGC Trust University Bangladesh, Chittagong, 4000, Bangladesh.
Ismat Ara
IA
Ishat
Department of Pharmacy, University of Chittagong, Chittagong, 4331, Bangladesh. nasirmir@cu.ac.bd.
Mir Muhammad Nasir
MM
Uddin
D000251:Adenosine Triphosphatases / Q000737:chemistry* / Q000378:metabolism*; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism; D019295:Computational Biology / Q000379:methods*; D062105:Molecular Docking Simulation; D010802:Phylogeny; D011550:Pseudomonas aeruginosa / Q000201:enzymology*; D000069296:Type III Secretion Systems / Q000378:metabolism*
D001426:Bacterial Proteins; D000069296:Type III Secretion Systems; D000251:Adenosine Triphosphatases
ATPase; Phylogenetic analysis; Pseudomonas aeruginosa; Salicylidene acylhydrazide; Type III secretion system