In silico analyses of isoniazid and streptomycin resistance-associated mutations in Mycobacterium tuberculosis.

ABSTRACT: Multi-drug resistant tuberculosis is categorised by the World Health Organisation (WHO) as a public health crisis. In silico techniques were used to probe the structural basis of Mycobacterium tuberculosis resistance to isoniazid and streptomycin. Isoniazid resistance-associated mutations in InhA were predicted to reduce the binding affinity of NADH to InhA, without affecting INH-NAD (competitive-inhibitor) binding. Perturbation of the mutated residues was predicted (with the AlloSigMA server) to modulate the free energy of allosteric modulation of key binding site residues F41, F149, Y158 and W222. These results suggest that allosteric modulation of the protein structure may be key to the mechanism by which isoniazid resistance-associated mutations act. Mutations in the meth

SUBMITTER: Dasoondi RS 

PROVIDER: S-EPMC10006719 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature