Probing conformational plasticity of the activation domain of trypsin: the role of glycine hinges

Biochemistry
Linda GombosLászló Gráf

Abstract

Trypsin-like serine proteases play essential roles in diverse physiological processes such as hemostasis, apoptosis, signal transduction, reproduction, immune response, matrix remodeling, development, and differentiation. All of these proteases share an intriguing activation mechanism that involves the transition of an unfolded domain (activation domain) of the zymogen to a folded one in the active enzyme. During this conformational change, activation domain segments move around highly conserved glycine hinges. In the present study, hinge glycines were replaced by alanine residues via site directed mutagenesis. The effects of these mutations on the interconversion of the zymogen-like and active conformations as well as on catalytic activity were studied. Mutant trypsins showed zymogen-like structures to varying extents characterized by increased flexibility of some activation domain segments, a more accessible N-terminus and a deformed substrate binding site. Our results suggest that the trypsinogen to trypsin transition is hindered by the mutations, which results in a shift of the equilibrium between the inactive zymogen-like and active enzyme conformations toward the inactive state. Our data also showed, however, that the ina...Continue Reading

References

Apr 16, 1998·Biochimica Et Biophysica Acta·S J Hubbard
Jan 15, 2000·The Journal of Biological Chemistry·S BraudA Wisner
Feb 6, 2002·Journal of Molecular Biology·Gergely KatonaLászló Szilágyi
Jul 20, 2002·Blood Reviews·James Uprichard, David J Perry

❮ Previous
Next ❯

Citations

Nov 21, 2012·Briefings in Functional Genomics·Merse E Gáspár, Peter Csermely
Jul 21, 2012·Biochemistry. Biokhimii︠a︡·A A Zamyatnin, O L Voronina
Jun 24, 2014·Journal of Hazardous Materials·Yan-Qing WangZhenghao Fei
Jan 8, 2016·International Journal of Biological Macromolecules·Xiangrong Li, Mingjiang Geng
Oct 12, 2013·Biophysical Chemistry·Austin D VogtEnrico Di Cera
Jun 6, 2012·Current Opinion in Structural Biology·Nicola PozziEnrico Di Cera
Jul 6, 2011·Trends in Biotechnology·David W Gohara, Enrico Di Cera
Sep 12, 2015·Luminescence : the Journal of Biological and Chemical Luminescence·Xiangrong Li, Peihong Li
Aug 21, 2013·Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy·Hongmei ZhangYanqing Wang
May 11, 2011·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Anna Á RauscherAndras Malnasi-Csizmadia
Dec 15, 2020·Biophysics Reviews·Enrico Di Cera
May 7, 2021·Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy·Xiangrong LiYongtao Xu
Aug 8, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Jiayin LiuAoxue Wang
Aug 21, 2013·Biochemistry·Austin D Vogt, Enrico Di Cera

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Related Papers

The Journal of Biological Chemistry
Alaji BahEnrico Di Cera
Cellular and Molecular Life Sciences : CMLS
M E PapaconstantinouEnrico Di Cera
© 2021 Meta ULC. All rights reserved