6jd0

Structure of mutant human cathepsin L, engineered for GAG binding

spinqualitylabelsall models 6jd0, resolution 1.81Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6jd0 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 1.805Å Ligands: CL, EDO, EOH, GOL, NA, PGE, PO4, POL Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function CATL1_HUMAN Important for the overall degradation of proteins in lysosomes. Publication Abstract from PubMed Engineering precise substrate specificity of proteases advances the potential to use them in biotechnological and therapeutic applications. Collagen degradation, a physiological process mediated by collagenases, is an integral part of extracellular matrix remodeling and when uncontrolled, implicated in different pathological conditions. Lysosomal cathepsin-K cleaves triple helical collagen fiber, whereas cathepsin-L cannot do so. In this study, we have imparted collagenolytic property to cathepsin-L, by systematically engineering proline-specificity and glycosaminoglycans (GAG)-binding surface in the protease. The proline-specific mutant shows high specificity for prolyl-peptidic substrate but is incapable of cleaving collagen. Engineering a GAG-binding surface on the proline-specific mutant enabled it to degrade type-I collagen in the presence of chondroitin-4-sulfate (C4-S). We also present the crystal structures of proline-specific (1.4 A) and collagen-specific (1.8 A) mutants. Finally docking studies with prolyl-peptidic substrate (Ala-Gly-Pro-Arg-Ala) at the active site and a C4-S molecule at the GAG-binding site enable us to identify key structural features responsible for collagenolytic activity of cysteine cathepsins. Structure-guided protein engineering of human cathepsin L for efficient collagenolytic activity.,Choudhury D, Biswas S Protein Eng Des Sel. 2021 Feb 15;34. pii: 6213762. doi: 10.1093/protein/gzab005. PMID:33825882 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Cathepsin 3D structures

Proteopedia Page Contributors and Editors (what is this?)

OCA