Structural highlights
Function
[TLDD_ECOLI] Metalloprotease involved in CcdA degradation. Suppresses the inhibitory activity of the carbon storage regulator (CsrA).[1] [PMBA_ECOLI] Metalloprotease involved in CcdA degradation. Suppresses the inhibitory activity of the carbon storage regulator (CsrA).[2]
Publication Abstract from PubMed
TldD and TldE proteins are involved in the biosynthesis of microcin B17 (MccB17), an Escherichia coli thiazole/oxazole-modified peptide toxin targeting DNA gyrase. Using a combination of biochemical and crystallographic methods we show that E. coli TldD and TldE interact to form a heterodimeric metalloprotease. TldD/E cleaves the N-terminal leader sequence from the modified MccB17 precursor peptide, to yield mature antibiotic, while it has no effect on the unmodified peptide. Both proteins are essential for the activity; however, only the TldD subunit forms a novel metal-containing active site within the hollow core of the heterodimer. Peptide substrates are bound in a sequence-independent manner through beta sheet interactions with TldD and are likely cleaved via a thermolysin-type mechanism. We suggest that TldD/E acts as a "molecular pencil sharpener": unfolded polypeptides are fed through a narrow channel into the active site and processively truncated through the cleavage of short peptides from the N-terminal end.
The Origins of Specificity in the Microcin-Processing Protease TldD/E.,Ghilarov D, Serebryakova M, Stevenson CEM, Hearnshaw SJ, Volkov D, Maxwell A, Lawson DM, Severinov K Structure. 2017 Sep 11. pii: S0969-2126(17)30259-9. doi:, 10.1016/j.str.2017.08.006. PMID:28943336[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Allali N, Afif H, Couturier M, Van Melderen L. The highly conserved TldD and TldE proteins of Escherichia coli are involved in microcin B17 processing and in CcdA degradation. J Bacteriol. 2002 Jun;184(12):3224-31. PMID:12029038
- ↑ Allali N, Afif H, Couturier M, Van Melderen L. The highly conserved TldD and TldE proteins of Escherichia coli are involved in microcin B17 processing and in CcdA degradation. J Bacteriol. 2002 Jun;184(12):3224-31. PMID:12029038
- ↑ Ghilarov D, Serebryakova M, Stevenson CEM, Hearnshaw SJ, Volkov D, Maxwell A, Lawson DM, Severinov K. The Origins of Specificity in the Microcin-Processing Protease TldD/E. Structure. 2017 Sep 11. pii: S0969-2126(17)30259-9. doi:, 10.1016/j.str.2017.08.006. PMID:28943336 doi:http://dx.doi.org/10.1016/j.str.2017.08.006
