Factor active site blocked

IFN-ot stimulates MHC class I expression by upregulating transcription through the ISRE site of the MHC class I promoter (Ting and Baldwin 1993 van den Elsen et al. 1998). Northern blot analyses demonstrate that HCMV infection blocks IFN-y-stimulated MHC class I expression in infected fibroblasts and ECs (Miller et al. 1999). Moreover, gene expression and EMSA analyses reveal that IFN-ot-stimulated IRF-1 expression and transcription factor activation are blocked in HCMV-infected cells, a phenotype similar to the block in IFN-y-stimulated responses in HCMV-infected cells (Miller et al. 1999). 

It has become apparent that the method of crosslinking can dramatically affect the activity of an immunotoxin in vivo. This is true not only with regard to possible direct blocking by the crosslinker of the enzymatic active site which is responsible for inactivation of ribosomes, but the chemistry of conjugation also is an important factor in proper binding and entry of the... 

While the x-ray structure of native Factor Xa has been reported [4] the nature of its crystal packing, specifically the fact that the active site of one Factor Xa molecule is blocked by the N-terminus of a second resulting in a continuous polymeric structure, apparently has precluded diffusing inhibitors into the preformed crystals to obtain complexes. Complexes with inhibitors cocrystallized with Factor Xa also have not been reported [81]. Thus, efforts to do structure-based design with this enzyme have relied on molecular modeling. 

Antifibrinolytic compounds can block the conversion of plasminogen to plasmin, or directly bind to the active site of plasmin to inhibit fibrinolysis. The plasma protein, a 2-macroglobulin, is a primary physiological inhibitor of plasmin. Plasmin released from fibrin is also very rapidly inactivated by a2-antiplasmin, which plays a role in the regulation of the fibrinolytic process (Aoki and Harpel, 1984). 2-anti plasmin inactivates plasmin in a very rapid reaction, interferes with plasminogen binding to fibrin, and is ligated to fibrin by Factor Xllla (Sakata and Aoki, 1980). After a2-antiplasmin is covalendy linked to fibrin s G-terminal a chain, it retains it ability to inhibit plasmin, a function that helps to prevent premature clot lysis. 

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