ABSTRACT
MfpA protein encoded by Mycobacterium tuberculosis (Mtb) and stands for Mycobacterium fluoroquinolone resistance protein A. This protein provides Mtb intrinsic resistant property from fluoroquinolone antibiotics by inhibiting DNA gyrase that are known to be the primary target of fluoroquinolone drugs. DNA gyrases are important for bacterial chromosomal genesis as they are majorly involved in DNA replication, transcription, bacterial stress response to several external stimulus. Therefore, in Mtb it forms an essential integrity and also a desirable target for drug development approaches. This article implies on determining the essential facts about mfpA including its interaction study, epitope prediction, modelling and validation and most importantly it deals with the mutation. Mutational analysis was carried out on the basis of sequential information and there were several mutations that cause a large decrease in stability of the protein. Total 24 mutations were shortlisted based on ΔΔG value W154G, F54G, L84G, F9G, W4G, F74G, F64G, F49G, L104G, L94G, L124G, F29G, L39G, L59G, W60G, L114G, W154G, W154S, L19G, L144G, L129G, F34G, W154D, W154A and W4S. Separate mutation on DXXG GTPase motif was examined to check any effect on protein stability and we found that D33A, D98A, D128A, G36A, G101A, G131A, D33G, D98G, D128G, G36W, G101W, G131W, D33K, D98K, D128K decreases protein stability the most. Further stress dependent analysis on selected residues showed that lower temperature and pH destabilizes the protein. The reason behind this increase in protein destability was drastic decrease and disruption of interatomic interactions in mutant MfpA. This analysis provides essential information about the residues that are important for MfpA stability and also enlightens protein vulnerability after mutation. This article is protected by copyright. All rights reserved.