Molecular mechanisms of serpin deficiencies

The study of serpin deficiency is currently one of the most active areas in basic medical research. Recently, three hypotheses concerning serpin defic iency have been proposed, which are referred to as the conformational distu rbance hypothesis (CDH), loop-sheet polymerisation hypothesis (LSPH) and mu ltiple binding site hypothesis (MBSH). CDH was put forward to explicit serp in deficiency due to conformational change of reactive loop of serpins as a result of mutations occurring away from the reactive site residues and LSP H was to explain deficient serpins due to the formation of polymers. MBSH w as proposed to explain the mechanism of the formation of stable enzyme-serp in complex via more than one binding site and blockage or mutation in any o f the sites resulting in serpin deficiency. A combination of these mechanis ms may be critical in understanding the roles of the many documented mutati ons and autoimmunities which result in qualitative and quantitative serpin deficiency.