Stiffness of the C-terminal disordered linker affects the geometry of the active site in endoglucanase Cel8A. Issue 12 (29th September 2016)

• Record Type: Journal Article
• Authors: Różycki, Bartosz; Cieplak, Marek
• Is Part Of: Molecular bioSystems. Volume 12:Issue 12(2016:Dec.)
• Page Start: 3589
• Page End: 3599
• Publication Date: 2016-09-29
• Subjects: Molecular biology -- Periodicals; Biochemistry -- Periodicals; 571.7405
• DOI: 10.1039/c6mb00606j
• Languages: English
• ISSNs: 1742-206X

Abstract

Abstract : Stiffness of disordered linkers affects the conformation of the active-site cleft when Cel8A is bound to its substrate. Abstract : Cellulosomes are complex multi-enzyme machineries which efficiently degrade plant cell-wall polysaccharides. The multiple domains of the cellulosome proteins are often tethered together by intrinsically disordered regions. The properties and functions of these disordered linkers are not well understood. In this work, we study endoglucanase Cel8A, which is a relevant enzymatic component of the cellulosomes of Clostridium thermocellum . We use both all-atom and coarse-grained simulations to investigate how the conformations of the catalytic domain of Cel8A are affected by the disordered linker at its C terminus. We find that when the endoglucanase is bound to its substrate, the effective stiffness of the linker can influence the distances between groups of amino-acid residues throughout the entire enzymatic domain. In particular, variations in the linker stiffness can lead to small changes in the geometry of the active-site cleft. We suggest that such geometrical changes may have an effect on the catalytic activity of the enzyme.