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The mature bovine cathepsin C (CC) molecule is composed of four identical monomers, each proteolytically processed into three chains. Five intrachain disulfides and three nonpaired cysteine residues per monomer were identified. Beside catalytic Cys234 in the active site, free-thiol Cys331 and Cys424 were characterized. Cys424 can be classified as inaccessible buried residue. Selective modification of Cys331 results in dissociation of native CC tetramer into dimers. The 3D homology-based model of the CC catalytic core suggests that Cys331 becomes exposed as the activation peptide is removed during procathepsin C activation. The model further shows that exposed Cys331 is surrounded by a surface hydrophobic cluster, unique to CC, forming a dimer-dimer interaction interface. Substrate/inhibitor recognition of the active site in the CC dimer differs significantly from that in the native tetramer. Taken together, a mechanism is proposed that assumes that the CC tetramer formation results in a site-specific occlusion of endopeptidase-like active site cleft of each CC monomeric unit. Thus, tetramerization provides for the structural basis of the dipeptidyl peptidase activity of CC through a substrate access-limiting mechanism different from those found in homologous monomeric exopeptidases cathepsin H and B. In conclusion, the mechanism of tetramer formation as well as specific posttranslational processing segregates CC in the family of papain proteases.

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PMgUe, Ci%XhOdOveki8Abafrad. Crude Van Dyke protein prepared from frozen bovine posterior pituitary glands WBB treated with formic acid to reletme small bound and &orbed peptides. Gel filtration, continuous free-flow eledrophoreais and descending paper electrophoresis were need to separate the amall ptides into successively purer fractions which were a m a x f o r preaeor, uterotonk, natriuretic and mehnocyte stimdating acthitien under double blind conditions. The higheat peak of natriuretio activity was ~eeociated with ody 8 small premor and no uterotonic activities, and the name fractions contained a ninhydrin-positive spot on paper electrophoresis, the mobility stimulating hormone (MSH) and A(;TH-( 1-13-amide)-tridecapeptide (1-13 ACI'H-amide) but differed fmm v wpreaein and oxytocin. Material from this spot had an amino Of Which a t pH 5.6 W8d Simik that Of 8lph8-mel8mCyte acid composition which comsponded with the first 13 residues of ACI'H. Qoantitativs biosMsy of the fins1 fraction in the frog demonstrated a melanotropic sctivity which, however, wan lower than would have been expected for p m alpha-MSH.The natriuretic activity of the isolated fraction wan far higher than the potency of separately adminiatemd peptidee which might be present ' ' e-vampreasin, alpha-MSH or 1-13 mixture of alpha-biSH and 1-13 A m , and that alpha-MSH may be an scetylsted end-product of ACI!H cleavage in the pituitary.Key wor&: A(;TH fragments, alpha-MSH, natriuretic peptiden, natriuretic hormone. ACTH. It is s n g g 2 3 -that the isolated fraction represents aThere is an extensive literature over the past decade concerning the appearance of a natriuretic activity in blood plesma and urine during natriuretic states in many mammalian species, induced by such stimuli as: saline, dextran or blood infusion, carotid occlusion, etc. The physiological evidence has been reviewed

The methylamide Nα-phenylthiocarbamoyl derivatives of encoded amino acids II were prepared either by the addition of phenylisothiocyanate to amino acid methylamides or by the treatment of amino acid phenylthiohydantoins (5-alkyl-3-phenyl-2-thioxo-4-imidazolinones) I with methylamine. The derivatives were prepared of 19 amino acids and their melting points, 1H NMR, 13C NMR, mass, ultraviolet and infrared spectra were measured.