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PDBsum entry 4q80
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Hydrolase/hydrolase inhibitor
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PDB id
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4q80
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References listed in PDB file
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Key reference
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Title
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Structures of neutrophil serine protease 4 reveal an unusual mechanism of substrate recognition by a trypsin-Fold protease.
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Authors
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S.J.Lin,
K.C.Dong,
C.Eigenbrot,
M.Van lookeren campagne,
D.Kirchhofer.
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Ref.
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Structure, 2014,
22,
1333-1340.
[DOI no: ]
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PubMed id
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Abstract
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Trypsin-fold proteases, the largest mammalian protease family, are classified by
their primary substrate specificity into one of three categories, trypsin-like,
chymotrypsin-like, and elastase-like, based on key structural features of their
active site. However, the recently discovered neutrophil serine protease 4
(NSP4, also known as PRSS57) presents a paradox: NSP4 exhibits a trypsin-like
specificity for cleaving substrates after arginine residues, but it bears
elastase-like specificity determining residues in the active site. Here we show
that NSP4 has a fully occluded S1 pocket and that the substrate P1-arginine
adopts a noncanonical "up" conformation stabilized by a
solvent-exposed H-bond network. This uncommon arrangement, conserved in all NSP4
orthologs, enables NSP4 to process substrates after both arginine as well as
post-translationally modified arginine residues, such as methylarginine and
citrulline. These findings establish a distinct paradigm for substrate
recognition by a trypsin-fold protease and provide insights into the function of
NSP4.
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