7jl7

Zebrafish Caspase N213TZebrafish Caspase N213T

Structural highlights 7jl7 is a 5 chain structure with sequence from Danio rerio 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 2.05Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A0A2R8QUC0_DANRE Publication Abstract from PubMed Caspase (or cysteinyl-aspartate specific proteases) enzymes play important roles in apoptosis and inflammation, and the non-identical but overlapping specificity profiles (that is, cleavage recognition sequence) direct cells to different fates. Although all caspases prefer aspartate at the P1 position of the substrate, the caspase-6 subfamily shows preference for valine at the P4 position, while caspase-3 shows preference for aspartate. In comparison with human caspases, caspase-3a from zebrafish has relaxed specificity and demonstrates equal selection for either valine or aspartate at the P4 position. In the context of the caspase-3 conformational landscape, we show that changes in hydrogen bonding near the S3 subsite affect selection of the P4 amino acid. Swapping specificity with caspase-6 requires accessing new conformational space, where each landscape results in optimal binding of DxxD (caspase-3) or VxxD (caspase-6) substrate and simultaneously disfavors binding of the other substrate. Within the context of the caspase-3 conformational landscape, substitutions near the active site result in nearly equal activity against DxxD and VxxD by disrupting a hydrogen bonding network in the substrate binding pocket. The converse substitutions in zebrafish caspase-3a result in increased selection for P4 aspartate over valine. Overall, the data show that the shift in specificity that results in a dual function protease, as in zebrafish caspase-3a, requires fewer amino acid substitutions compared with those required to access new conformational space for swapping substrate specificity, such as between caspases-3 and -6. Remodeling hydrogen bond interactions results in relaxed specificity of Caspase-3.,Yao L, Swartz P, Hamilton PT, Clark AC Biosci Rep. 2021 Jan 29;41(1):BSR20203495. doi: 10.1042/BSR20203495. PMID:33448281 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

spinqualitylabelsall models 7jl7, resolution 2.05Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image