4q7z

Neutrophil serine protease 4 (PRSS57) with phe-phe-arg-chloromethylketone (FFR-cmk)

spinqualitylabelsall models 4q7z, resolution 1.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4q7z is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.4Å Ligands: 2YT, CL, FUC, GOL, NAG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function PRS57_HUMAN Publication Abstract from PubMed 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. Structures of Neutrophil Serine Protease 4 Reveal an Unusual Mechanism of Substrate Recognition by a Trypsin-Fold Protease.,Lin SJ, Dong KC, Eigenbrot C, van Lookeren Campagne M, Kirchhofer D Structure. 2014 Aug 19. pii: S0969-2126(14)00238-X. doi:, 10.1016/j.str.2014.07.008. PMID:25156428 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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