Cystatin inhibition of cathepsin B requires dislocation of the proteinase occluding loop. Demonstration by release of loop anchoring through mutation of His110

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• 作者：Pavlova ; Alla ; Krupa ; Joanne C. ; Mort ; John S. ; Abrahamson ; Magnus ; Bjö ; rk ; Ingemar
• 关键词：Cysteine proteinase ; Cysteine proteinase inhibitor ; Cathepsin ; Cystatin ; Stopped-flow kinetics ; C29A-cathepsin B ; cathepsin B variant in which Cys29 is replaced by Ala ; DTT ; dithiothreitol ; H110A/C29A-cathepsin B ; C29A-cathepsin B variant in which His110
• 刊名：FEBS Letters
• 出版年：2000
• 出版时间：December 29, 2000
• 年：2000
• 卷：487
• 期：2
• 页码：156-160
• 全文大小：88.6 K

文摘

Cystatins A and C were both shown to inhibit cathepsin B by a two-step mechanism, involving an initial weak interaction followed by a conformational change. Disruption of the major salt bridge anchoring the occluding loop of cathepsin B to the main body of the enzyme by mutation of His110 to Ala converted the binding to an apparent one-step reaction. The second step of cystatin binding to cathepsin B must therefore be due to the inhibitor having to alter the conformation of the enzyme by displacing the occluding loop to allow a tight complex to be formed. Cystatin A was appreciably less effective in displacing the loop than cystatin C, resulting in a considerably lower overall inhibition rate constant.