NMR STUDIES OF A BLOOD COAGULATION FACTOR INHIBITOR

本研究计划旨在阐明结构功能 负责CMTI-V的选择性抑制的关系 胰蛋白酶和其它丝氨酸蛋白酶，如因子XII，一种血- 凝血因子（Hageman因子）。 此外，差分 在酶中起作用的相互作用：形成抑制剂复合物 通过完整的CMTI-V和反应位点水解的CMTI-V（CMTI-V）， 胰蛋白酶和因子XII也将被表征。 CMTI-V分离 并首次在PI的实验室中进行了表征。 其主要 由68个氨基酸残基组成的结构，包括二硫化物 桥，已经确定。 在一项合作努力中，CMTI-V已经 克隆并在大肠杆菌中过表达。 此外，一个变种人 也制备了（T43A），其显示出降低的抑制水平， 对胰蛋白酶的活性。 从我们目前的研究中获得的知识可能 帮助设计更好的治疗策略， 紊乱

This research program is aimed at elucidating structure function relationships that are responsible for CMTI-V's selective inhibition of trypsin and other serine proteinases such as Factor XII, a blood- coagulation factor (Hageman Factor). In addition, differential interactions that come into play in the enzyme:inhibitor complexes formed by intact CMTI-V and reactive-site hydrolyzed CMTI-V (CMTI-V) with trypsin and Factor XII, will also be characterized. CMTI-V was isolated and characterized for the first time in the PI's laboratory. Its primary structures consisting of 68 amino acid residues including a disulfide bridge, has been determined. In a collaborative effort, CMTI-V has been cloned and overexpressed in Escherichia coli. Furthermore, a mutant has also been prepared (T43A) which shows a reduced level of inhibitory activity toward trypsin. Knowledge gained from our present study may help design better therapeutic strategies for treating blood coagulation disorders.