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

Physical Chemistry Chemical Physics : PCCP
Rodrigo L Silveira, Munir S Skaf

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 exhibits 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 the loop motions of the 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 a substrate, the characteristic large amplitude dynamics of TrCel7A consists of breathing motions, where the loops undergo open-and-close fluctuations. Upon substrate binding, the open-close fluctuations of the loops 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 o...Continue Reading

References

Dec 1, 1993·Proteins·A AmadeiH J Berendsen
Jan 31, 1997·The Journal of Biological Chemistry·S ArmandH Driguez
Jul 23, 2004·The Journal of Chemical Physics·Donald HamelbergJ Andrew McCammon
Nov 16, 2004·Biophysical Journal·Alejandra Leo-MaciasAngel R Ortiz
Jun 28, 2005·Nucleic Acids Research·John C GordonAlexey Onufriev
Oct 14, 2005·Journal of Computational Chemistry·James C PhillipsKlaus Schulten
Jul 22, 2008·Proceedings of the National Academy of Sciences of the United States of America·Sara E DobbinsMichael J E Sternberg
Feb 21, 2009·Journal of Computational Chemistry·L MartínezJ M Martínez
Feb 18, 2010·Journal of Chemical Theory and Computation·Olgun GuvenchAlexander D Mackerell
May 28, 2010·Biotechnology and Bioengineering·Jürgen Jalak, Priit Väljamäe
Nov 6, 2010·The Journal of Biological Chemistry·Mihhail Kurasin, Priit Väljamäe
Dec 22, 2010·Chemical Society Reviews·Lars KonermannYu-Hong Liu
Jun 21, 2011·Computational Science & Discovery·Yi WangJ Andrew McCammon
Sep 3, 2011·Science·Kiyohiko IgarashiMasahiro Samejima
Jan 1, 2011·Annual Review of Chemical and Biomolecular Engineering·Shishir P S ChundawatBruce E Dale
Sep 18, 2012·Journal of Chemical Theory and Computation·Levi C T PierceRoss C Walker
Jun 5, 2013·Proceedings of the National Academy of Sciences of the United States of America·Marcelo KernSimon J McQueen-Mason
Feb 28, 2014·Journal of the American Chemical Society·Akihiko NakamuraMasahiro Samejima
May 28, 2014·Current Opinion in Biotechnology·Gregg T BeckhamChristina M Payne
Apr 30, 1998·The Journal of Physical Chemistry. B·A D MacKerellM Karplus
Dec 2, 2014·The Journal of Physical Chemistry. B·Rodrigo L Silveira, Munir S Skaf
Jan 30, 2015·Chemical Reviews·Christina M PayneGregg T Beckham
Aug 25, 2015·Biotechnology and Bioengineering·Meera E AtreyaDouglas S Clark

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Citations

Nov 2, 2019·Proceedings of the National Academy of Sciences of the United States of America·Josh V VermaasBrandon C Knott
Nov 23, 2019·Biotechnology for Biofuels·Marcelo Ventura RubioAndré Damasio
Jul 8, 2019·Biochimica Et Biophysica Acta. Proteins and Proteomics·Carlos Eduardo PenaPaulo Ricardo Batista
Jul 4, 2021·The Journal of Biological Chemistry·Japheth E GadoChristina M Payne

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Methods Mentioned

BETA
atomic force microscopy
transmission electron microscopy
AFM
small
angle neutron scattering
PCA
glycosylation

Software Mentioned

CHARMM
PCA
Packmol

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