Structural highlights
FunctionCATL1_HUMAN Important for the overall degradation of proteins in lysosomes. Publication Abstract from PubMedEngineering 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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