6NTW

Crystal structure of E. coli YcbB

Summary for 6NTW

• Entry DOI: 10.2210/pdb6ntw/pdb
• Descriptor: Probable L,D-transpeptidase YcbB, (2S,3R,4S)-4-{[(3S,5R)-5-(dimethylcarbamoyl)pyrrolidin-3-yl]sulfanyl}-2-[(2S,3R)-3-hydroxy-1-oxobutan-2-yl]-3-methyl-3,4-dihydro-2H-pyrrole-5-carboxylic acid, SULFATE ION, ... (4 entities in total)
• Functional Keywords: l, d-transpeptidase, transferase, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Escherichia coli (strain K12)
• Total number of polymer chains: 1
• Total formula weight: 65531.03

Authors

Caveney, N.A.,Strynadka, N.C.J.,Caballero, G.,Worrall, L.J. (deposition date: 2019-01-30, release date: 2019-03-20, Last modification date: 2024-11-20)

Primary citation

Caveney, N.A.,Caballero, G.,Voedts, H.,Niciforovic, A.,Worrall, L.J.,Vuckovic, M.,Fonvielle, M.,Hugonnet, J.E.,Arthur, M.,Strynadka, N.C.J.
Structural insight into YcbB-mediated beta-lactam resistance in Escherichia coli.
Nat Commun, 10:1849-1849, 2019

PubMed Abstract: The bacterial cell wall plays a crucial role in viability and is an important drug target. In Escherichia coli, the peptidoglycan crosslinking reaction to form the cell wall is primarily carried out by penicillin-binding proteins that catalyse D,D-transpeptidase activity. However, an alternate crosslinking mechanism involving the L,D-transpeptidase YcbB can lead to bypass of D,D-transpeptidation and beta-lactam resistance. Here, we show that the crystallographic structure of YcbB consists of a conserved L,D-transpeptidase catalytic domain decorated with a subdomain on the dynamic substrate capping loop, peptidoglycan-binding and large scaffolding domains. Meropenem acylation of YcbB gives insight into the mode of inhibition by carbapenems, the singular antibiotic class with significant activity against L,D-transpeptidases. We also report the structure of PBP5-meropenem to compare interactions mediating inhibition. Additionally, we probe the interaction network of this pathway and assay beta-lactam resistance in vivo. Our results provide structural insights into the mechanism of action and the inhibition of L,D-transpeptidation, and into YcbB-mediated antibiotic resistance.

PubMed: 31015395
DOI: 10.1038/s41467-019-09507-0

Experimental method

X-RAY DIFFRACTION (2.76 Å)