Prioritization of Mur family drug targets against A. baumannii and identification of their homologous proteins through molecular phylogeny, primary sequence, and structural analysis

Gizachew Muluneh Amera; Rameez Jabeer Khan; Rajat Kumar Jha; Amita Pathak; Jayaraman Muthukumaran; Amit Kumar Singh

doi:10.1186/s43141-020-00048-4

Prioritization of Mur family drug targets against A. baumannii and identification of their homologous proteins through molecular phylogeny, primary sequence, and structural analysis

J Genet Eng Biotechnol. 2020 Jul 28;18(1):33. doi: 10.1186/s43141-020-00048-4.

Authors

Gizachew Muluneh Amera¹, Rameez Jabeer Khan¹, Rajat Kumar Jha¹, Amita Pathak², Jayaraman Muthukumaran¹, Amit Kumar Singh³

Affiliations

¹ Department of Biotechnology, School of Engineering and Technology, Sharda University, Greater Noida, UP, 201310, India.
² Department of Chemistry, Indian Institute of Technology, Hauz Khas, New Delhi, 110016, India.
³ Department of Biotechnology, School of Engineering and Technology, Sharda University, Greater Noida, UP, 201310, India. amitk.singh@sharda.ac.in.

Abstract

Background: The World Health Organization (WHO) report stated that Acinetobacter baumannii had been classified as one of the most important pathogenic bacteria causing nosocomial infection in hospital patients due to multi-drug resistance (MDR). It is vital to find out new bacterial drug targets and annotated their structure and function for the exploration of new anti-bacterial agents. The present study utilized a systematic route to prioritize the potential drug targets that belong to Mur family of Acinetobacter baumannii and identify their homologous proteins using a computational approach such as sequence similarity search, multiple sequence alignment, phylogenetic analysis, protein sequence, and protein structure analysis.

Results: From the results of protein sequence analysis of eight Mur family proteins, they divided into three main enzymatic classes namely transferases (MurG, MurA and MraY), ligases (MurC, MurD, MurE, and MurF), and oxidoreductase (MurB). Based on the results of intra-comparative protein sequence analysis and enzymatic classification, we have chosen MurB, MurE, and MurG as the prioritized drug targets from A. baumannii and subjected them for further detailed studies of inter-species comparison. This inter-species comparison help us to explore the sequential and structural properties of homologous proteins in other species and hence, opens a gateway for new target identification and using common inhibitor for different bacterial species caused by various diseases. The pairwise sequence alignment results between A. baumannii's MurB with A. calcoaceticus's MurB, A. baumannii's MurE with A. seifertii's MurE, and A. baumannii's MurG with A. pittii's MurG showed that every group of the proteins are highly similar with each other and they showed sequence identity of 95.7% and sequence similarity of 97.2%.

Conclusion: Together with the results of secondary and three-dimensional structure predictions explained that three selected proteins (MurB, MurE, and MurG) from A. baumannii and their related proteins (AcMurB, AsMurE, and ApMurG) belong to mixed αβ class and they are very similar.

Keywords: 3D structure; Acinetobacter baumannii; Drug targets Secondary structure; Molecular phylogeny; Primary sequence.