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Concerted motions and large scale structural fluctuations of Trichoderma reesei Cel7A cellobiohydrolase

Abstract

Cellobiohydrolases (CBHs) are key enzymes for the saccharification of cellulose and play major roles in industrial settings for biofuel production. The catalytic core domain of these enzymes exhibit a long and narrow binding tunnel capable of binding glucan chains from crystalline cellulose and processively hydrolyze them. The binding cleft is topped by a set of loops, which are believed to play key roles in substrate binding and cleavage processivity. Here, we present an analysis of loop motions of Trichoderma reesei Cel7A catalytic core domain (TrCel7A) using conventional and accelerated molecular dynamics simulations. We observe that the loops exhibit highly coupled fluctuations and cannot move independently of each other. In the absence of substrate, the characteristic large amplitude dynamics of TrCel7A consists of breathing motions, where the loops undergo open-and-close fluctuations. Upon substrate binding, the loops open-close fluctuations are quenched and one of the loops moves parallel to the binding site, possibly to allow processive motion along the glucan chain. Using microsecond accelerated molecular dynamics, we observe large-scale fluctuations of the loops (up to 37 Å) and the entire exposure of TrCel7A binding site in absence of substrate, resembling an endoglucanase. These results suggest that the initial CBH-substrate contact and substrate recognition by the enzyme are similar to that of endoglucanases and, once bound to the substrate, the loops remain closed for proper enzymatic activity.

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Publication details

The article was received on 05 Jan 2018, accepted on 09 Feb 2018 and first published on 09 Feb 2018


Article type: Paper
DOI: 10.1039/C8CP00101D
Citation: Phys. Chem. Chem. Phys., 2018, Accepted Manuscript
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    Concerted motions and large scale structural fluctuations of Trichoderma reesei Cel7A cellobiohydrolase

    R. L. Silveira and M. S. Skaf, Phys. Chem. Chem. Phys., 2018, Accepted Manuscript , DOI: 10.1039/C8CP00101D

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