Dynamics of Ligand Binding to a Rigid Glycosidase

Fredj Ben Bdira; Christopher A. Waudby; Alexander N. Volkov; Sybrin P. Schröder; A. B. Eiso; Jeroen D. C. Codée; Hermen S. Overkleeft; Johannes M. F. G. Aerts; Hugo van Ingen; Marcellus Ubbink

doi:10.1002/anie.202003236

Dynamics of Ligand Binding to a Rigid Glycosidase

Fredj Ben Bdira
, Christopher A. Waudby
, Alexander N. Volkov
, Sybrin P. Schröder
, A. B. Eiso
, Jeroen D. C. Codée
, Hermen S. Overkleeft
, Johannes M. F. G. Aerts
, Hugo van Ingen
, Marcellus Ubbink^*

^*Corresponding author for this work

Leiden University
University College London
Vrije Universiteit Brussel
ZoBio BV, BioPartner 2 building, J.H. Oortweg 19, 2333 CH, Leiden, The Netherlands
Utrecht University

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

The single-domain GH11 glycosidase from Bacillus circulans (BCX) is involved in the degradation of hemicellulose, which is one of the most abundant renewable biomaterials in nature. We demonstrate that BCX in solution undergoes minimal structural changes during turnover. NMR spectroscopy results show that the rigid protein matrix provides a frame for fast substrate binding in multiple conformations, accompanied by slow conversion, which is attributed to an enzyme-induced substrate distortion. A model is proposed in which the rigid enzyme takes advantage of substrate flexibility to induce a conformation that facilitates the acyl formation step of the hydrolysis reaction.

Original language	English
Pages (from-to)	20508-20514
Number of pages	7
Journal	Angewandte Chemie (International ed. in English)
Volume	59
Issue number	46
Early online date	2020
DOIs	https://doi.org/10.1002/anie.202003236 https://doi.org/10.1002/ange.202003236
Publication status	Published - 9 Nov 2020
Externally published	Yes

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This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 7 Affordable and Clean Energy

Keywords

NMR spectroscopy
dynamics
glycosidases
ligand binding
rigid fold

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title = "Dynamics of Ligand Binding to a Rigid Glycosidase",

abstract = "The single-domain GH11 glycosidase from Bacillus circulans (BCX) is involved in the degradation of hemicellulose, which is one of the most abundant renewable biomaterials in nature. We demonstrate that BCX in solution undergoes minimal structural changes during turnover. NMR spectroscopy results show that the rigid protein matrix provides a frame for fast substrate binding in multiple conformations, accompanied by slow conversion, which is attributed to an enzyme-induced substrate distortion. A model is proposed in which the rigid enzyme takes advantage of substrate flexibility to induce a conformation that facilitates the acyl formation step of the hydrolysis reaction.",

keywords = "NMR spectroscopy, dynamics, glycosidases, ligand binding, rigid fold",

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doi = "10.1002/anie.202003236",

language = "English",

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T1 - Dynamics of Ligand Binding to a Rigid Glycosidase

AU - Ben Bdira, Fredj

AU - Waudby, Christopher A.

AU - Volkov, Alexander N.

AU - Schröder, Sybrin P.

AU - Eiso, A. B.

AU - Codée, Jeroen D. C.

AU - Overkleeft, Hermen S.

AU - Aerts, Johannes M. F. G.

AU - van Ingen, Hugo

AU - Ubbink, Marcellus

PY - 2020/11/9

Y1 - 2020/11/9

N2 - The single-domain GH11 glycosidase from Bacillus circulans (BCX) is involved in the degradation of hemicellulose, which is one of the most abundant renewable biomaterials in nature. We demonstrate that BCX in solution undergoes minimal structural changes during turnover. NMR spectroscopy results show that the rigid protein matrix provides a frame for fast substrate binding in multiple conformations, accompanied by slow conversion, which is attributed to an enzyme-induced substrate distortion. A model is proposed in which the rigid enzyme takes advantage of substrate flexibility to induce a conformation that facilitates the acyl formation step of the hydrolysis reaction.

AB - The single-domain GH11 glycosidase from Bacillus circulans (BCX) is involved in the degradation of hemicellulose, which is one of the most abundant renewable biomaterials in nature. We demonstrate that BCX in solution undergoes minimal structural changes during turnover. NMR spectroscopy results show that the rigid protein matrix provides a frame for fast substrate binding in multiple conformations, accompanied by slow conversion, which is attributed to an enzyme-induced substrate distortion. A model is proposed in which the rigid enzyme takes advantage of substrate flexibility to induce a conformation that facilitates the acyl formation step of the hydrolysis reaction.

KW - NMR spectroscopy

KW - dynamics

KW - glycosidases

KW - ligand binding

KW - rigid fold

UR - https://www.scopus.com/pages/publications/85090150429

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DO - 10.1002/anie.202003236

M3 - Article

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SN - 1433-7851

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JO - Angewandte Chemie (International ed. in English)

JF - Angewandte Chemie (International ed. in English)

IS - 46

ER -

Dynamics of Ligand Binding to a Rigid Glycosidase

Abstract

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Keywords

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