Plasma protease inhibitors in mouse and man: divergence within the reactive centre regions.

Article Details

Citation

Hill RE, Shaw PH, Boyd PA, Baumann H, Hastie ND

Plasma protease inhibitors in mouse and man: divergence within the reactive centre regions.

Nature. 1984 Sep 13-19;311(5982):175-7.

PubMed ID
6547997 [ View in PubMed
]
Abstract

The plasma protease inhibitors control a wide variety of physiological functions including blood coagulation, complement activation and aspects of the inflammatory response. The inhibitors function by forming a 1:1 complex with a specific protease within the reactive centre region of the inhibitor. Little is known about the evolutionary relationships of these inhibitors. We report here the sequences of cDNAs which represent the C-terminal halves of the two major murine plasma protease inhibitors. One of these, murine alpha 1-antitrypsin, more appropriately called alpha 1-proteinase inhibitor (alpha 1-PI), has diverged from its human counterpart at a vital position in the reactive centre but this has not led to a physiologically significant change in function. Also, we have determined the partial sequence of a recently characterized protein termed contrapsin, which inhibits trypsin-like proteases. We show, surprisingly, that contrapsin is highly homologous to human alpha 1-antichymotrypsin, an inhibitor of chymotrypsin-like proteases. The reactive centre regions of these two inhibitors have diverged considerably, which may account for the differences in specificity. We propose that the genes for contrapsin and human alpha 1-antichymotrypsin are the descendents of a single gene that have evolved since rodent and primate divergence to encode proteins with different functions.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Alpha-1-antichymotrypsinP01011Details