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Proteases act in important homeostatic pathways and are tightly regulated. Here, we report an unusual structural mechanism of regulation observed by the 2.5-[Angstrom] X-ray crystal structure of the serine protease, granzyme C. Although the active-site triad residues adopt canonical conformations, the oxyanion hole is improperly formed, and access to the primary specificity (S1) pocket is blocked through a reversible rearrangement involving Phe-191. Specifically, a register shift in the 190-strand preceding the active-site serine leads to Phe-191 filling the S1 pocket. Mutation of a unique Glu--Glu motif at positions 192-193 unlocks the enzyme, which displays chymase activity, and proteomic analysis confirms that activity of the wild-type protease can be released through interactions with an appropriate substrate. The 2.5-[Angstrom] structure of the unlocked enzyme reveals unprecedented flexibility in the 190-strand preceding the active-site serine that results in Phe-191 vacating the S1 pocket. Overall, these observations describe a broadly applicable mechanism of protease regulation that cannot be predicted by template-based modeling or bioinformatic approaches alone. protease regulation | register shift | allostery

Research reveals that chimeras of the alpha(sub)1-antitrypsin efficiently inhibit papain-like cysteine protease and that the inhibition is a function of the length of the reactive center loop. Data indicate that the inhibition requires insertion of the reactive center loop into the body of the cysteine protease body.

The mouse SQN-5 serpin inhibits both chymotrypsin-like serine and the papain-like cysteine proteinases through a reactive site loop-dependent inhibitory mechanism. Data indicate that the human and mouse serpin genes seem to have originated from a common ancestor.

Research has been conducted on the members of the serpine family human squamous cell carcinoma antigens (SCCA) 1 and 2. The SCCA1 inhibition mechanism is described.

The revision of the Elley-Irving Socio-Economic Index based on the statistics derived from the 2001 Census of New Zealand is described. The occupations, in this census, are scaled according to the average income and educational levels of full-time male workers in each occupation.

Research has been conducted on serpin superfamily member hurpin, linked to human keratinocyte apoptosis. Results deminstrate that hurpin is an inhibitor of the archetypal lysosome cysteine proteinase cathepsin L.

The Standards Committee of the American Correctional Assn was organized to continually review correction standards and to evaluate whether its standards are relevant to current trends in correction management. The Committee has 20 members which serve for six years. The members are knowledgable in all aspects of corrections management, from adult, juvenile, courts, jails, probation and parole. The Committee announces suggested standards revisions and asks comments from all sectors concerned before making decisions.