4WVJ: Crystal structure of the Type-I signal peptidase from Staphylococcus aureus (SpsB) in complex with an inhibitor peptide (pep3)

Bacterial type I signal peptidases (SPases) are membrane-anchored serine proteases that process the signal peptides of proteins exported via the Sec and Tat secretion systems. Despite their crucial importance for bacterial virulence and their attractiveness as drug targets, only one such enzyme, LepB from Escherichia coli, has been structurally characterized, and the transient nature of peptide binding has stymied attempts to directly visualize SPase-substrate complexes. Here, the crystal structure of SpsB, the type I signal peptidase from the Gram-positive pathogen Staphylococcus aureus, is reported, and a peptide-tethering strategy that exploits the use of carrier-driven crystallization is described. This enabled the determination of the crystal structures of three SpsB-peptide complexes, both with cleavable substrates and with an inhibitory peptide. SpsB-peptide interactions in these complexes are almost exclusively limited to the canonical signal-peptide motif Ala-X-Ala, for which clear specificity pockets are found. Minimal contacts are made outside this core, with the variable side chains of the peptides accommodated in shallow grooves or exposed faces. These results illustrate how high fidelity is retained despite broad sequence diversity, in a process that is vital for cell survival.
PDB ID: 4WVJDownload
MMDB ID: 132805
PDB Deposition Date: 2014/11/5
Updated in MMDB: 2017/12
Experimental Method:
x-ray diffraction
Resolution: 1.95  Å
Source Organism:
Staphylococcus aureus subsp. aureus COL
Similar Structures:
Biological Unit for 4WVJ: dimeric; determined by author and by software (PISA)
Molecular Components in 4WVJ
Label Count Molecule
Proteins (2 molecules)
Maltose-binding Periplasmic Protein,signal Peptidase IB(Gene symbol: malE)
Molecule annotation
Inhibitor Peptide (Pep3)
Molecule annotation
Chemical (1 molecule)
* Click molecule labels to explore molecular sequence information.

Citing MMDB