7q8f

Peptide GNYKEAKK in complex with human cathepsin V C25A mutant

spinqualitylabelsall models 7q8f, resolution 1.49Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7q8f is a 4 chain structure with sequence from Homo sapiens 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 1.49Å Ligands: ACE, CL, GOL, MPD, NH2, TFA Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Addressing the elusive specificity of cysteine cathepsins, which in contrast to caspases and trypsin-like proteases lack strict specificity determining P1 pocket, calls for innovative approaches. Proteomic analysis of cell lysates with human cathepsins K, V, B, L, S, and F identified 30,000 cleavage sites, which we analyzed by software platform SAPS-ESI (Statistical Approach to Peptidyl Substrate-Enzyme Specific Interactions). SAPS-ESI is used to generate clusters and training sets for support vector machine learning. Cleavage site predictions on the SARS-CoV-2 S protein, confirmed experimentally, expose the most probable first cut under physiological conditions and suggested furin-like behavior of cathepsins. Crystal structure analysis of representative peptides in complex with cathepsin V reveals rigid and flexible sites consistent with analysis of proteomics data by SAPS-ESI that correspond to positions with heterogeneous and homogeneous distribution of residues. Thereby support for design of selective cleavable linkers of drug conjugates and drug discovery studies is provided. Proteomic data and structure analysis combined reveal interplay of structural rigidity and flexibility on selectivity of cysteine cathepsins.,Tusar L, Loboda J, Impens F, Sosnowski P, Van Quickelberghe E, Vidmar R, Demol H, Sedeyn K, Saelens X, Vizovisek M, Mihelic M, Fonovic M, Horvat J, Kosec G, Turk B, Gevaert K, Turk D Commun Biol. 2023 Apr 24;6(1):450. doi: 10.1038/s42003-023-04772-8. PMID:37095140 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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