6ube

Azide-triggered subtilisin SUBT_BACAM complexed with the peptide LFRAL

spinqualitylabelsall models 6ube, resolution 1.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6ube is a 2 chain structure with sequence from Bacillus amyloliquefaciens and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.6Å Ligands: AZI, GOL, NA Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed We describe the design, kinetic properties, and structures of engineered subtilisin proteases that degrade the active form of RAS by cleaving a conserved sequence in switch 2. RAS is a signaling protein that, when mutated, drives a third of human cancers. To generate high specificity for the RAS target sequence, the active site was modified to be dependent on a cofactor (imidazole or nitrite) and protease sub-sites were engineered to create a linkage between substrate and cofactor binding. Selective proteolysis of active RAS arises from a 2-step process wherein sub-site interactions promote productive binding of the cofactor, enabling cleavage. Proteases engineered in this way specifically cleave active RAS in vitro, deplete the level of RAS in a bacterial reporter system, and also degrade RAS in human cell culture. Although these proteases target active RAS, the underlying design principles are fundamental and will be adaptable to many target proteins. Engineering subtilisin proteases that specifically degrade active RAS.,Chen Y, Toth EA, Ruan B, Choi EJ, Simmerman R, Chen Y, He Y, Wang R, Godoy-Ruiz R, King H, Custer G, Travis Gallagher D, Rozak DA, Solomon M, Muro S, Weber DJ, Orban J, Fuerst TR, Bryan PN Commun Biol. 2021 Mar 5;4(1):299. doi: 10.1038/s42003-021-01818-7. PMID:33674772 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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