Cysteine Proteinases and Their Inhibitors A Traditional Topic of the Portoroz Conferences
Cysteine Proteinases and Their Inhibitors A Traditional Topic of the Portoroz Conferences
复制标题
半胱氨酸蛋白酶及其抑制剂是 Portoroz 会议的传统主题
作者：
H. Fritz;M. Jochum
在Vito Turk的实验室中分离出来的一种蛋白质导致了半胱氨酸蛋白酶抑制剂超家族的发现。Werner Machleidt的小组与Werner Müller-Esterl一起证明，激肽原具有半胱氨酸蛋白酶抑制剂的作用。在80年代中期，当蛋白质测序被DNA测序迅速取代时，Werner Machleidt开始研究半胱氨酸蛋白酶及其抑制剂的功能。他再次从改进现有的酶/抑制动力学方法开始。他引入了具有在线数字数据收集功能的灵敏连续测定法，可以精确表征紧密结合抑制剂。使用Ennes Auerswald在Hans Fritz实验室生产的重组半胱氨酸蛋白酶抑制剂变体的工作证实并扩展了Wolfram Bode小组获得的半胱氨酸蛋白酶和半胱氨酸蛋白酶抑制剂晶体结构所假设的抑制机制。与Marianne Jochum一起，组织蛋白酶B在多发性创伤和腹膜炎患者的临床研究中被确定为炎症的重要标志物。针对肿瘤细胞的细胞周组织蛋白酶B的合成抑制剂和亲和标记物已经与Louis Moroder的小组一起设计和评估。最近，表面等离子体共振技术（BIACORE）已成功地用于研究蛋白酶抑制剂的相互作用。目前，Werner Machleidt领导着一个活跃的研究小组，致力于研究钙蛋白酶及其蛋白抑制剂，钙蛋白酶抑制剂和激肽原。他的研究课题包括结构-功能关系和分子机制，以及钙蛋白酶/钙蛋白酶抑制蛋白系统的细胞定位及其在细胞凋亡中的作用。
that had been isolated in Vito Turk ́s laboratory led to the discovery of the superfamily of cystatins. Together with Werner Müller-Esterl, it was shown in Werner Machleidt ́s group that the kininogens function as cysteine proteinase inhibitors. In the middle of the 80`s, when protein sequencing was rapidly superseded by DNA sequencing, Werner Machleidt began to study the functions of cysteine proteinases and their inhibitors. Again he started with improvements of the existing methodology of enzyme/inhibition kinetics. He introduced sensitive continuous assays with online digital data collection that allow the precise characterisation of tight-binding inhibitors. Work using recombinant cystatin variants produced by Ennes Auerswald in Hans Fritz ́ laboratory confirmed and extended the mechanisms of inhibition postulated from the crystal structures of cysteine proteinases and cystatins obtained in Wolfram Bode ́s group. Together with Marianne Jochum, cathepsin B was identified as an important marker of inflammation in clinical studies of polytrauma and peritonitis patients. Synthetic inhibitors and affinity labels directed against pericellular cathepsin B of tumor cells have been designed and evaluated together with Louis Moroder ́s group. Recently, the surface plasmon resonance technology (BIACORE) has successfully been utilized to study proteinase-inhibitor interactions. Currently, Werner Machleidt leads an active research group working on calpains and their protein inhibitors, calpastatin and kininogen. His research topics range from structure-function relationships and molecular mechanisms to the cellular localization of the calpain/calpastatin system and its role in apoptosis.