Covariation analysis of the master bacterial DNA replication initiator DnaA. Issue 5 (27th May 2022)

• Record Type: Journal Article
• Authors: Dobby, Laura; Murray, Heath
• Is Part Of: Access microbiology. Volume 4:Issue 5(2022)
• Publication Date: 2022-05-27
• Subjects: Microbiology -- Periodicals; 579
• DOI: 10.1099/acmi.ac2021.po0148
• Languages: English
• ISSNs: 2516-8290

Abstract

Abstract : Bacterial DNA replication initiation is governed by DnaA: an oligomeric protein belonging to the ATPases associated with diverse cellular activities (AAA+) superfamily. The master replication initiator is present in all known bacterial pathogens; thus, it is an attractive target for drug discovery. Here, an in-silico evolutionary covariation analysis of DnaA amino acid residues was conducted using EVcouplings, a Python framework, to investigate connections between key protein residues. Several co-evolving amino acid pairs were identified and characterized using PyMol to visualize the residues on DnaA crystal structures. I hypothesize that some co-evolving pairs, particularly those spatially connected, are likely important for structural integrity of the protein. Interestingly, one co-evolving pair of residues (A. aeolicus Val121 and Ser229) was found to be separated by ~27 angstroms, suggesting a more complex relationship connects these two sites. Thus, analysing co-evolution of DnaA residues supports known structural information and may predict either allosteric connections within DnaA or contacts between DnaA and other binding partners.