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6JD0

Structure of mutant human cathepsin L, engineered for GAG binding

Summary for 6JD0
Entry DOI10.2210/pdb6jd0/pdb
DescriptorCathepsin L1, GLYCEROL, CHLORIDE ION, ... (10 entities in total)
Functional Keywordscathepsin l, collagenase, gag, hydrolase
Biological sourceHomo sapiens (Human)
Total number of polymer chains1
Total formula weight45008.26
Authors
Choudhury, D.,Biswas, S. (deposition date: 2019-01-30, release date: 2020-02-05, Last modification date: 2024-10-30)
Primary citationChoudhury, D.,Biswas, S.
Structure-guided protein engineering of human cathepsin L for efficient collagenolytic activity.
Protein Eng.Des.Sel., 34:-, 2021
Cited by
PubMed Abstract: 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 Å) and collagen-specific (1.8 Å) 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.
PubMed: 33825882
DOI: 10.1093/protein/gzab005
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (1.805 Å)
Structure validation

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