The calcium ion was proposed to be involved in protein structure stabilization against thermal and proteolytic degradation, such as autolysis phenomena, in trypsin-like serine proteases. However, molecular details related to the role played by the metal ion are still largely unknown. Several molecular dynamics simulations of 6 ns have been used to investigate the dynamic behavior of bovine and salmon trypsins in calcium-bound and calcium-free forms, with the aim of evaluating the role of the calcium ion in trypsin three-dimensional structure and autoproteolysis propensity. It turned out that the calcium-free trypsins are characterized by a more flexible structure, revealing structure-function relationships connecting Ca<sup>2+</sup> binding and autoproteolysis propensity. In particular, the removal of Ca<sup>2+</sup> not only increases the flexibility of regions around its binding site, in the N-terminal domain, but also leads to channeling of the fluctuations to remote sites in the C-terminal domain, possibly involving the interdomain loop. Two primary autolysis sites are strongly influenced by calcium binding (R117 and K188) in bovine trypsin, whereas Ca<sup>2+</sup> plays a less crucial role in salmon trypsin. © 2005 American Chemical Society.

Papaleo, E., Fantucci, P., & DE GIOIA, L. (2005). Effects of Calcium Binding on Structure and Autolysis Regulation in Trypsins. A Molecular Dynamics Investigation. JOURNAL OF CHEMICAL THEORY AND COMPUTATION, 1(6), 1286-1297 [10.1021/ct050092o].

Effects of Calcium Binding on Structure and Autolysis Regulation in Trypsins. A Molecular Dynamics Investigation

PAPALEO, ELENA;FANTUCCI, PIERCARLO;DE GIOIA, LUCA
2005

Abstract

The calcium ion was proposed to be involved in protein structure stabilization against thermal and proteolytic degradation, such as autolysis phenomena, in trypsin-like serine proteases. However, molecular details related to the role played by the metal ion are still largely unknown. Several molecular dynamics simulations of 6 ns have been used to investigate the dynamic behavior of bovine and salmon trypsins in calcium-bound and calcium-free forms, with the aim of evaluating the role of the calcium ion in trypsin three-dimensional structure and autoproteolysis propensity. It turned out that the calcium-free trypsins are characterized by a more flexible structure, revealing structure-function relationships connecting Ca2+ binding and autoproteolysis propensity. In particular, the removal of Ca2+ not only increases the flexibility of regions around its binding site, in the N-terminal domain, but also leads to channeling of the fluctuations to remote sites in the C-terminal domain, possibly involving the interdomain loop. Two primary autolysis sites are strongly influenced by calcium binding (R117 and K188) in bovine trypsin, whereas Ca2+ plays a less crucial role in salmon trypsin. © 2005 American Chemical Society.
Articolo in rivista - Articolo scientifico
Scientifica
protein chemistry
English
Papaleo, E., Fantucci, P., & DE GIOIA, L. (2005). Effects of Calcium Binding on Structure and Autolysis Regulation in Trypsins. A Molecular Dynamics Investigation. JOURNAL OF CHEMICAL THEORY AND COMPUTATION, 1(6), 1286-1297 [10.1021/ct050092o].
Papaleo, E; Fantucci, P; DE GIOIA, L
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/10281/14050
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