4k1s

Gly-Ser-SplB protease from Staphylococcus aureus at 1.96 A resolution

spinqualitylabelsall models 4k1s, resolution 1.96Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4k1s is a 2 chain structure with sequence from Staphylococcus aureus subsp. aureus NCTC 8325. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function SPLB_STAA8 Serine protease that cleaves specifically after the sequence Trp-Glu-Leu-Gln. Publication Abstract from PubMed Staphylococcal SplB protease belongs to the chymotrypsin family. Chymotrypsin zymogen is activated by proteolytic processing at the N terminus, resulting in significant structural rearrangement at the active site. Here, we demonstrate that the molecular mechanism of SplB protease activation differs significantly and we characterize the novel mechanism in detail. Using peptide and protein substrates we show that the native signal peptide, or any N-terminal extension, has an inhibitory effect on SplB. Only precise N-terminal processing releases the full proteolytic activity of the wild type analogously to chymotrypsin. However, comparison of the crystal structures of mature SplB and a zymogen mimic show no rearrangement at the active site whatsoever. Instead, only the formation of a unique hydrogen bond network, distant form the active site, by the new N-terminal glutamic acid of mature SplB is observed. The importance of this network and influence of particular hydrogen bond interactions at the N terminus on the catalytic process is demonstrated by evaluating the kinetics of a series of mutants. The results allow us to propose a consistent model where changes in the overall protein dynamics rather than structural rearrangement of the active site are involved in the activation process. Staphylococcal SplB Serine Protease Utilizes a Novel Molecular Mechanism of Activation.,Pustelny K, Zdzalik M, Stach N, Stec-Niemczyk J, Cichon P, Czarna A, Popowicz G, Mak P, Drag M, Salvesen GS, Wladyka B, Potempa J, Dubin A, Dubin G J Biol Chem. 2014 May 30;289(22):15544-53. doi: 10.1074/jbc.M113.507616. Epub, 2014 Apr 8. PMID:24713703 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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