[Truncated abstract] Introduction of stabilising disulphide bonds into periplasmic proteins is catalysed by oxidoreductases (DsbA), a process essential for virulence in all Gram negative bacteria. Many bacteria possess a single oxidoreductase that donates disulphides to all host proteins containing multiple cysteines. However, an increasing number of organisms have been shown to contain multiple oxidoreductases. In these instances, it appears that these enzymes preferentially insert disulphide bonds into a select number of substrate proteins. This has led to the hypothesis that some oxidoreductases have a broad substrate recognition profile, whilst others have a narrow substrate recognition profile. However, the mechanisms underpinning these observations regarding these different groups of oxidoreductases remain unknown. Neisseria meningitidis contains three oxidoreductases known as NmDsbA1, NmDsbA2 and NmDsbA3. NmDsbA1 and NmDsbA2 share 78% amino acid homology and have been shown to insert disulphide bonds into a selection of protein substrates including the major pilin subunit, PilE, and the secretin, PilQ. NmDsbA3, which has only 50% amino acid homology with NmDsbA1 and NmDsbA2, is unable to catalyse disulphide bond donation to PilE or PilQ. Because all three oxidoreductases are chromosomally encoded, we hypothesised that changes in the structure and function of these oxidoreductases would be due to co-evolution of these three genes within N. meningitidis. Therefore, we hypothesised that a comparison of the structure and function of these three oxidoreductases may reveal further information regarding substrate recognition by these enzymes...
|Qualification||Doctor of Philosophy|
|Publication status||Unpublished - 2011|