5NJ5

E. coli Microcin-processing metalloprotease TldD/E with phosphate bound

Summary for 5NJ5

• Entry DOI: 10.2210/pdb5nj5/pdb
• Descriptor: Metalloprotease TldD, Metalloprotease PmbA, ZINC ION, ... (6 entities in total)
• Functional Keywords: metalloprotease, microcin, ccda, dna gyrase, hydrolase
• Biological source: Escherichia coli str. K-12 substr. MG1655; More
• Cellular location: Cytoplasm: P0AFK0
• Total number of polymer chains: 4
• Total formula weight: 204091.60

Authors

Ghilarov, D.,Serebryakova, M.,Stevenson, C.E.M.,Hearnshaw, S.J.,Volkov, D.,Maxwell, A.,Lawson, D.M.,Severinov, K. (deposition date: 2017-03-28, release date: 2017-10-04, Last modification date: 2024-01-17)

Primary citation

Ghilarov, D.,Serebryakova, M.,Stevenson, C.E.M.,Hearnshaw, S.J.,Volkov, D.S.,Maxwell, A.,Lawson, D.M.,Severinov, K.
The Origins of Specificity in the Microcin-Processing Protease TldD/E.
Structure, 25:1549-1561.e5, 2017

PubMed Abstract: 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 β 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.

PubMed: 28943336
DOI: 10.1016/j.str.2017.08.006

Experimental method

X-RAY DIFFRACTION (1.9 Å)