Structural bioinformatic analysis of DsbA proteins and their pathogenicity associated substrates

• Published in: Computational and structural biotechnology journal Vol. 19; pp. 4725 - 4737
• Main Authors: Santos-Martin, Carlos, Wang, Geqing, Subedi, Pramod, Hor, Lilian, Totsika, Makrina, Paxman, Jason John, Heras, Begoña
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.01.2021; Research Network of Computational and Structural Biotechnology; Elsevier
• Subjects: Antimicrobials; Disulfide bond; Oxidoreductase; Protein-protein interactions; Review; Thioredoxin proteins; Disulfide bond; Oxidoreductase; Antimicrobials; Protein-protein interactions; Thioredoxin proteins
• ISSN: 2001-0370; 2001-0370
• DOI: 10.1016/j.csbj.2021.08.018

[Display omitted] The disulfide bond (DSB) forming system and in particular DsbA, is a key bacterial oxidative folding catalyst. Due to its role in promoting the correct assembly of a wide range of virulence factors required at different stages of the infection process, DsbA is a master virulence rheostat, making it an attractive target for the development of new virulence blockers. Although DSB systems have been extensively studied across different bacterial species, to date, little is known about how DsbA oxidoreductases are able to recognize and interact with such a wide range of substrates. This review summarizes the current knowledge on the DsbA enzymes, with special attention on their interaction with the partner oxidase DsbB and substrates associated with bacterial virulence. The structurally and functionally diverse set of bacterial proteins that rely on DsbA-mediated disulfide bond formation are summarized. Local sequence and secondary structure elements of these substrates are analyzed to identify common elements recognized by DsbA enzymes. This not only provides information on protein folding systems in bacteria but also offers tools for identifying new DsbA substrates and informs current efforts aimed at developing DsbA targeted anti-microbials.