5DIR

membrane protein at 2.8 Angstroms

Summary for 5DIR

• Entry DOI: 10.2210/pdb5dir/pdb
• Related PRD ID: PRD_002257
• Descriptor: Lipoprotein signal peptidase, Globomycin, (2R)-2,3-dihydroxypropyl (9Z)-octadec-9-enoate, ... (4 entities in total)
• Functional Keywords: membrane protein, protease, antibiotic, complex, hydrolase
• Biological source: Pseudomonas aeruginosa (strain ATCC 15692 / PAO1 / 1C / PRS 101 / LMG 12228); More
• Total number of polymer chains: 8
• Total formula weight: 95465.92

Authors

Vogeley, L.,El Arnaout, T.,Bailey, J.,Boland, C.,Caffrey, M. (deposition date: 2015-09-01, release date: 2016-03-02, Last modification date: 2024-10-09)

Primary citation

Vogeley, L.,El Arnaout, T.,Bailey, J.,Stansfeld, P.J.,Boland, C.,Caffrey, M.
Structural basis of lipoprotein signal peptidase II action and inhibition by the antibiotic globomycin.
Science, 351:876-880, 2016

PubMed Abstract: With functions that range from cell envelope structure to signal transduction and transport, lipoproteins constitute 2 to 3% of bacterial genomes and play critical roles in bacterial physiology, pathogenicity, and antibiotic resistance. Lipoproteins are synthesized with a signal peptide securing them to the cytoplasmic membrane with the lipoprotein domain in the periplasm or outside the cell. Posttranslational processing requires a signal peptidase II (LspA) that removes the signal peptide. Here, we report the crystal structure of LspA from Pseudomonas aeruginosa complexed with the antimicrobial globomycin at 2.8 angstrom resolution. Mutagenesis studies identify LspA as an aspartyl peptidase. In an example of molecular mimicry, globomycin appears to inhibit by acting as a noncleavable peptide that sterically blocks the active site. This structure should inform rational antibiotic drug discovery.

PubMed: 26912896
DOI: 10.1126/science.aad3747

Experimental method

X-RAY DIFFRACTION (2.8 Å)