title: Caught in the act: the crystal structure of cleaved cathepsin L bound to the active site of Cathepsin L.
abstract: Cathepsin L is a ubiquitously expressed papain-like cysteine protease involved in the endosomal degradation of proteins and has numerous roles in physiological and pathological processes, such as arthritis, osteoporosis, and cancer. Insight into the specificity of cathepsin L is important for elucidating its physiological roles and drug discovery. To study interactions with synthetic ligands, we prepared a presumably inactive mutant and crystallized it. Unexpectedly, the crystal structure determined at 1.4 Å revealed that the cathepsin L molecule is cleaved, with the cleaved region trapped in the active site cleft of the neighboring molecule. Hence, the catalytic mutant demonstrated low levels of catalytic activity.
authors.affiliation: Centre of Excellence for Integrated Approaches in Chemistry and Biology of Proteins, Slovenia.|International Postgraduate School Jozef Stefan, Ljubljana, Slovenia.
authors.forename: Piotr
authors.initials: P
authors.lastname: Sosnowski
authors.affiliation: Centre of Excellence for Integrated Approaches in Chemistry and Biology of Proteins, Slovenia.|International Postgraduate School Jozef Stefan, Ljubljana, Slovenia.|Jozef Stefan Institute, Ljubljana, Slovenia.
authors.forename: Dušan
authors.initials: D
authors.lastname: Turk
mesh_terms: D020134:Catalytic Domain; D056668:Cathepsin L / Q000737:chemistry* / Q000378:metabolism*; D003460:Crystallization; D018360:Crystallography, X-Ray; D006801:Humans; D008958:Models, Molecular; D010455:Peptides / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism
chemical_list: D010455:Peptides; D011994:Recombinant Proteins; D056668:Cathepsin L
keywords: cathepsin; cysteine cathepsin; substrate interaction