Molecular defect in coagulation factor XFriuli results from a substitution of serine for proline at position 343.

摘要: ACTOR X IS A SERINE protease zymogen that plays F a pivotal role in blood coagulation.’ It can be activated physiologically by the extrinsic (factor VIIa/tissue factor complex) and intrinsic IXa/factor VIIIa pathways presence of calcium phospholipid nonphysiologically an enzyme Russell’s viper venom (RW). In all cases, activation to Xa entails cleavage same arginine-isoleucine bond near aminoterminal heavy chain X.’ Factor combines with Va on cell surfaces form macromolecular complex for prothrombin activation. The various molecular interactions defined X/Xa have served as means grouping aberrations associated deviant molecule^.^^^ One type is exemplified observations population patients Friuli region Italy who exhibit moderate bleeding tendency homozygous deficiency prolonged partial thromboplastin clotting times, which exhibited activity levels 4% 9% normal, but near-normal times RVV.’ Their plasma contains normal antigen.333‘ Three related had since early childhood, epitaxis, from gums, posttraumatic hemarthroses, after tooth extractions other surgical procedures. Those heterozygous XFrluh defect possess varying 32% 55% are usually asymptomatic. No gross structural differences were observed weight or immunochemical analyses between isolated variant protein.6 Purified X,,,,,, was at rate RW, reduced 98% 75% pathways, respectively. Small chromogenic substrates not cleaved efficiently XFnui,,6.7 fluorescence polarization studies suggested bound dansylated inhibitor properly oriented within active site XaFrlu,, generated thrombin only about one third Xa. Peptide explains previous discrete biochemical functional XFriuli X. mutation abolished HgiCl restriction present gene, this change constitutes basis convenient method screening individuals carrying defect. ProlineMJ conserved 5 serine superfamily belongs part 14-residue L**t**P****t*C motif occurs least 16 enzymes. Computer analysis suggests may essential aspect conformational features important properties well proteases. o 1991 American Society Hematology.