PDBsum entry 5a42

Hydrolase inhibitor

PDB id: 5a42

Contents

Protein chain

1597 a.a.

PDB id:

5a42

Name:

Hydrolase inhibitor

Title:

Cryo-em single particle 3d reconstruction of the native conformation of e. Coli alpha-2-macroglobulin (ecam)

Structure:

Uncharacterized lipoprotein yfhm. Chain: a. Fragment: residues 40-1653. Synonym: alpha-2-macroglobulin. Engineered: yes. Other_details: the expressed and purified sample contained the sequence gpm-a40 to p1653.

Source:

Escherichia coli k-12. Organism_taxid: 83333. Expressed in: escherichia coli. Expression_system_taxid: 469008.

Authors:

I.Garcia-Ferrer,P.Arede,J.Gomez-Blanco,D.Luque,S.Duquerroy, J.R.Caston,T.Goulas,F.X.Gomis-Ruth

Key ref:

I.Garcia-Ferrer et al. (2015). Structural and functional insights into Escherichia coli α2-macroglobulin endopeptidase snap-trap inhibition. Proc Natl Acad Sci U S A, 112, 8290-8295. PubMed id: 26100869 DOI: 10.1073/pnas.1506538112

Date:

04-Jun-15 Release date: 29-Jul-15

Protein chain

P76578  (YFHM_ECOLI) -  Alpha-2-macroglobulin from Escherichia coli (strain K12)

Seq: 1653 a.a.

Struc: 1597 a.a.

DOI no: 10.1073/pnas.1506538112

Proc Natl Acad Sci U S A 112:8290-8295 (2015)

PubMed id: 26100869

Structural and functional insights into Escherichia coli α2-macroglobulin endopeptidase snap-trap inhibition.

I.Garcia-Ferrer, P.Arêde, J.Gómez-Blanco, D.Luque, S.Duquerroy, J.R.Castón, T.Goulas, F.X.Gomis-Rüth.

ABSTRACT

The survival of commensal bacteria requires them to evade host peptidases. Gram-negative bacteria from the human gut microbiome encode a relative of the human endopeptidase inhibitor, α2-macroglobulin (α2M). Escherichia coli α2M (ECAM) is a ∼180-kDa multidomain membrane-anchored pan-peptidase inhibitor, which is cleaved by host endopeptidases in an accessible bait region. Structural studies by electron microscopy and crystallography reveal that this cleavage causes major structural rearrangement of more than half the 13-domain structure from a native to a compact induced form. It also exposes a reactive thioester bond, which covalently traps the peptidase. Subsequently, peptidase-laden ECAM is shed from the membrane and may dimerize. Trapped peptidases are still active except against very large substrates, so inhibition potentially prevents damage of large cell envelope components, but not host digestion. Mechanistically, these results document a novel monomeric "snap trap."