FUNCTIONAL IMPLICATIONS OF THE MODELED STRUCTURE OF MASPIN

The tumor suppressor maspin (mammary-specific serpin) is an unstable s erpin that does not undergo the stressed to relaxed transition typical of proteinase inhibitory serpins and, consequently, is not likely to function as a serine proteinase inhibitor, This suggests that the posi tioning and configuration of the reactive site loop (RSL) of maspin ar e likely to resemble those of ovalbumin, the best studied noninhibitor y serpin. Accordingly, the tertiary structure of maspin has been model ed on the crystal structure of native ovalbumin. Biochemical data and the modeled theoretical structure of maspin reveal the absence of disu lfide bonds in the molecule and the presence of an unstable RSL that a dopts a distorted helical structure, We confirm that the RSL is extrem ely sensitive to limited proteolysis and suggest that this may provide a structural basis for the proteolytic inactivation of maspin, a proc ess that is likely to modulate the activity of maspin in biological sy stems.