BACKGROUND: Granzyme B, one of the most abundant granzymes in cytotoxic T-lymphocyte (CTL) granules, and members of the caspase (cysteine aspartyl proteinases) family have a unique cleavage specificity for aspartic acid in P1 and play critical roles in the biochemical events that culminate in cell death. RESULTS: We have determined the three-dimensional structure of the complex of the human granzyme B with a potent tetrapeptide aldehyde inhibitor. The Asp-specific S1 subsite of human granzyme B is significantly larger and less charged than the corresponding Asp-specific site in the apoptosis-promoting caspases, and also larger than the corresponding subsite in rat granzyme B. CONCLUSIONS: The above differences account for the variation in substrate specificity among granzyme B, other serine proteases and the caspases, and enable the design of specific inhibitors that can probe the physiological functions of these proteins and the disease states with which they are associated.
BACKGROUND:Granzyme B, one of the most abundant granzymes in cytotoxic T-lymphocyte (CTL) granules, and members of the caspase (cysteine aspartyl proteinases) family have a unique cleavage specificity for aspartic acid in P1 and play critical roles in the biochemical events that culminate in cell death. RESULTS: We have determined the three-dimensional structure of the complex of the humangranzyme B with a potent tetrapeptide aldehyde inhibitor. The Asp-specific S1 subsite of humangranzyme B is significantly larger and less charged than the corresponding Asp-specific site in the apoptosis-promoting caspases, and also larger than the corresponding subsite in ratgranzyme B. CONCLUSIONS: The above differences account for the variation in substrate specificity among granzyme B, other serine proteases and the caspases, and enable the design of specific inhibitors that can probe the physiological functions of these proteins and the disease states with which they are associated.
Authors: Sai Chetan K Sukuru; Florian Nigsch; Jean Quancard; Martin Renatus; Rajiv Chopra; Natasja Brooijmans; Dmitri Mikhailov; Zhan Deng; Allen Cornett; Jeremy L Jenkins; Ulrich Hommel; John W Davies; Meir Glick Journal: Protein Sci Date: 2010-11 Impact factor: 6.725
Authors: Dion Kaiserman; Catherina H Bird; Jiuru Sun; Antony Matthews; Kheng Ung; James C Whisstock; Philip E Thompson; Joseph A Trapani; Phillip I Bird Journal: J Cell Biol Date: 2006-11-20 Impact factor: 10.539
Authors: Sarah E Stewart; Stephanie C Kondos; Antony Y Matthews; Michael E D'Angelo; Michelle A Dunstone; James C Whisstock; Joseph A Trapani; Phillip I Bird Journal: J Biol Chem Date: 2014-02-20 Impact factor: 5.157
Authors: Benjamin M Larimer; Eric Wehrenberg-Klee; Frank Dubois; Anila Mehta; Taylor Kalomeris; Keith Flaherty; Genevieve Boland; Umar Mahmood Journal: Cancer Res Date: 2017-05-01 Impact factor: 12.701
Authors: Gabriela Guimarães; Marco Túlio R Gomes; Priscila C Campos; Fabio V Marinho; Natan R G de Assis; Tatiana N Silveira; Sergio C Oliveira Journal: Infect Immun Date: 2018-02-20 Impact factor: 3.441
Authors: Danielle B Ulanet; Michael Torbenson; Chi V Dang; Livia Casciola-Rosen; Antony Rosen Journal: Proc Natl Acad Sci U S A Date: 2003-09-30 Impact factor: 11.205
Authors: Catherina H Bird; Jiuru Sun; Kheng Ung; Diana Karambalis; James C Whisstock; Joseph A Trapani; Phillip I Bird Journal: Mol Cell Biol Date: 2005-09 Impact factor: 4.272