- Rv2410c (DUF403 in Pfam 25) : An alpha-helical protein,called Alpha-E that contains an internal duplication with each repeat possessing conserved ER motifs. Click here to access a multiple alignment.
- Rv2411c (split as DUF404+DUF407 in Pfam 25): A circularly permuted peptide ligase of the ATP-grasp fold.
- Rv2409c, Rv2569c: Transglutaminases that could serve either as a peptidase or a classical transglutaminase.
- Rv2568c (DUF2248 in Pfam 25): A metallopeptidase-family peptidase.
- Rv2567: An inactive circularly permuted ATP-grasp fused to the Alpha-E domain.
- Rv2566 (Transglut+DUF2126 in Pfam 25): A transglutaminase fused to a circularly permuted peptide ligase of the COOH-NH2 ligase superfamily.
- Some species additionally contain an NTN hydrolase related to the proteasomal peptidase (called Anbu in one study) in the gene neighborhoods (not Mycobacterium) and amidotransferases of the GAT-I family. Click here to access all operons.
However, assembling the pieces of the puzzle together, we can be sure of a few things
- This is not involved in amino acid or glutathione biosynthesis. The species containing this system typically have intact pathways for glutathione or amino acid biosynthesis. Also there are no other genes suggestive of metabolic function in the neighborhood.
- It is not involved in the biosynthesis of a distinctive secondary metabolite such as an antibiotic or siderophore, for it lacks characteristic associations seen in these systems (see examples in our study of such systems).
- There is no evidence of a small protein that is conjugated to a target as in ubiquitination or pupylation.
|Gene neighborhoods of the novel system described in this post|
Alternatively, the transglutaminase superfamily protein might indeed function in cross-linking the peptide to lysine side chains or other amino groups. Thus, the weight of the contextual evidence supports a role for this widespread conserved gene-neighborhood in peptide synthesis; the resulting peptide could be added as a tag to the unique Alpha-E protein in this system.Such a tag could either regulate the assembly of complexes of the alpha-E domain protein via cross-linking or its interactions (e.g. as in tubulin) or serve as an amino acid storage mechanism. Yet, as you can see, certain details of this interesting pathway are in need of further investigation, but its widespread presence suggests that an important and exciting piece of biology awaits creative experimentalists...