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PDBsum entry 5a42
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Hydrolase inhibitor
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PDB id
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5a42
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References listed in PDB file
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Key reference
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Title
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Structural and functional insights into escherichia coli α2-Macroglobulin endopeptidase snap-Trap inhibition.
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Authors
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I.Garcia-Ferrer,
P.Arêde,
J.Gómez-Blanco,
D.Luque,
S.Duquerroy,
J.R.Castón,
T.Goulas,
F.X.Gomis-Rüth.
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Ref.
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Proc Natl Acad Sci U S A, 2015,
112,
8290-8295.
[DOI no: ]
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PubMed id
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Abstract
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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."
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