Avtor/Urednik		Štern, Igor
Naslov		Izražanje in biokemijska karakterizacija ugotovljenih mutant katepsina C pri človeku
Tip		monografija
Kraj izdaje		Ljubljana
Založnik		Univerza v Ljubljani, Medicinska fakulteta
Leto izdaje		2004
Obseg		str. 49
Jezik		slo
Abstrakt		Cathepsin C is a lysosomal cysteine protease with dipeptidyl peptidase activity and oligomeric structure. Studies of some hereditary disorders (Papillon-Lefevre syndrome, Heim-Munk sydrome, prepubertal periodontitis) revealed that these disorders are caused by mutations in the cathepsin C gene. To further elucidate the role of cathepsin C, we solved its crystal structure. In its active form, cathepsin C is a homotetramer with the active sites on the surface of the molecule exposed to the solvent, which is a special case among other oligomeric proteases with known structure. The structure also explained the selectivity mechanism for its exopeptidase activity: the exculsion domain (part of the proregion which remains bound in the tetramer after activation) covers some binding sites and thus allows binding of the substrate only from its N-terminus. In this way, we explained how can cathepsin C activate zymoges of serine proteases in the cells that paricipate in the cellular immune response. To further expain the biological role of cathepsin C, the discovered missense mutations are very helpful, for they cause the cathepsin C enzyme avtivity to change. Therefore, we expressed some of the misssense mutants, purified the protein and measured their enzyme activity using Gly-Phe-4MbetaNA as a substrate. Mutants D212Y and Y323C do not show virtualy any detectable enzyme activity, while the Y280F mutant shows the same activity as the native enzyme. (Abstract truncated at 2000 characters)
Deskriptorji		CATHEPSINS MOLECULAR CONFORMATION MUTATION DNA, COMPLEMENTARY BASE SEQUENCE POLYMERASE CHAIN REACTION RECOMBINANT PROTEINS