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PDBsum entry 5nct
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Hydrolase inhibitor
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PDB id
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5nct
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References listed in PDB file
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Key reference
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Title
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A structure-Derived snap-Trap mechanism of a multispecific serpin from the dysbiotic human oral microbiome.
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Authors
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T.Goulas,
M.Ksiazek,
I.Garcia-Ferrer,
A.M.Sochaj-Gregorczyk,
I.Waligorska,
M.Wasylewski,
J.Potempa,
F.X.Gomis-Rüth.
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Ref.
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J Biol Chem, 2017,
292,
10883-10898.
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PubMed id
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Abstract
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Enduring host-microbiome relationships are based on adaptive strategies within a
particular ecological niche.Tannerella forsythiais a dysbiotic member of
the human oral microbiome that inhabits periodontal pockets and contributes to
chronic periodontitis. To counteract endopeptidases from the host or microbial
competitors,T. forsythiapossesses a serpin-type proteinase inhibitor
called miropin. Although serpins from animals, plants, and viruses have been
widely studied, those from prokaryotes have received only limited attention.
Here we show that miropin uses the serpin-type suicidal mechanism. We found
that, similar to a snap trap, the protein transits from a metastable native form
to a relaxed triggered or induced form after cleavage of a reactive-site target
bond in an exposed reactive-center loop. The prey peptidase becomes covalently
attached to the inhibitor, is dragged 75 Å apart, and is irreversibly
inhibited. This coincides with a large conformational rearrangement of miropin,
which inserts the segment upstream of the cleavage site as an extra β-strand in
a central β-sheet. Standard serpins possess a single target bond and inhibit
selected endopeptidases of particular specificity and class. In contrast,
miropin uniquely blocked many serine and cysteine endopeptidases of disparate
architecture and substrate specificity owing to several potential target bonds
within the reactive-center loop and to plasticity in accommodating extra
β-strands of variable length. Phylogenetic studies revealed a patchy
distribution of bacterial serpins incompatible with a vertical descent model.
This finding suggests that miropin was acquired from the host through horizontal
gene transfer, perhaps facilitated by the long and intimate association ofT.
forsythiawith the human gingiva.
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