NDLI: The complete conformational free energy landscape of β-xylose reveals a two-fold catalytic itinerary for β-xylanases

Content Provider	Royal Society of Chemistry (RSC)
Author	Iglesias-Fernández, Javier Raich, Lluís Rovira, Carme Ardèvol, Albert
Copyright Year	2015
Abstract	Unraveling the conformational catalytic itinerary of glycoside hydrolases (GHs) is a growing topic of interest in glycobiology, with major impact in the design of GH inhibitors. β-xylanases are responsible for the hydrolysis of glycosidic bonds in β-xylans, a group of hemicelluloses of high biotechnological interest that are found in plant cell walls. The precise conformations followed by the substrate during catalysis in β-xylanases have not been unambiguously resolved, with three different pathways being proposed from structural analyses. In this work, we compute the conformational free energy landscape (FEL) of β-xylose to predict the most likely catalytic itineraries followed by β-xylanases. The calculations are performed by means of ab initio metadynamics, using the Cremer–Pople puckering coordinates as collective variables. The computed FEL supports only two of the previously proposed itineraries, 2SO → [2,5B]ǂ → 5S1 and 1S3 → [4H3]ǂ → 4C1, which clearly appear in low energy regions of the FEL. Consistently, 2SO and 1S3 are conformations preactivated for catalysis in terms of free energy/anomeric charge and bond distances. The results however exclude the OE → [OS2]ǂ → B2,5 itinerary that has been recently proposed for a family 11 xylanase. Classical and ab initio QM/MM molecular dynamics simulations reveal that, in this case, the observed OE conformation has been enforced by enzyme mutation. These results add a word of caution on using modified enzymes to inform on catalytic conformational itineraries of glycoside hydrolases.
Starting Page	1167
Ending Page	1177
Page Count	11
File Format	HTM / HTML PDF
ISSN	20416520
Volume Number	6
Issue Number	2
Journal	Chemical Science
DOI	10.1039/c4sc02240h
Language	English
Publisher	Royal Society of Chemistry
Access Restriction	Open
Subject Keyword	Free-electron laser Enzyme Molecular dynamics FEL Cremer Thermodynamic free energy Ab initio quantum chemistry methods Hydrolysis Glycosidic bond Glycobiology Xylanase Conformational isomerism Mutation Metadynamics
Content Type	Text
Resource Type	Article
Subject	Chemistry

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Conformational Itinerary of Sucrose During Hydrolysis by Retaining Amylosucrase

Computational mutagenesis reveals the role of active-site tyrosine in stabilising a boat conformation for the substrate: QM/MM molecular dynamics studies of wild-type and mutant xylanases

Mechanism of glycoside hydrolysis: A comparative QM/MM molecular dynamics analysis for wild type and Y69F mutant retaining xylanases

Comparison of Free Energy Surfaces Calculations from Ab Initio Molecular Dynamic Simulations at the Example of Two Transition Metal Catalyzed Reactions

Ab initio conformational study of two lewis x analogues (2000).

The GTPase hGBP1 converts GTP to GMP in two steps via proton shuttle mechanisms

Ab initio molecular dynamics study of the hydrolysis reaction of diborane

On the reactivity and selectivity of donor glycosides in glycochemistry and glycobiology: trapped covalent intermediates

Solvent Influence on Cellulose 1,4-β-Glycosidic Bond Cleavage: A Molecular Dynamics and Metadynamics Study

The complete conformational free energy landscape of β-xylose reveals a two-fold catalytic itinerary for β-xylanases

Similar Documents

Conformational Itinerary of Sucrose During Hydrolysis by Retaining Amylosucrase

Computational mutagenesis reveals the role of active-site tyrosine in stabilising a boat conformation for the substrate: QM/MM molecular dynamics studies of wild-type and mutant xylanases

Mechanism of glycoside hydrolysis: A comparative QM/MM molecular dynamics analysis for wild type and Y69F mutant retaining xylanases

Comparison of Free Energy Surfaces Calculations from Ab Initio Molecular Dynamic Simulations at the Example of Two Transition Metal Catalyzed Reactions

Ab initio conformational study of two lewis x analogues (2000).

The GTPase hGBP1 converts GTP to GMP in two steps via proton shuttle mechanisms

Ab initio molecular dynamics study of the hydrolysis reaction of diborane

On the reactivity and selectivity of donor glycosides in glycochemistry and glycobiology: trapped covalent intermediates

Solvent Influence on Cellulose 1,4-β-Glycosidic Bond Cleavage: A Molecular Dynamics and Metadynamics Study

The complete conformational free energy landscape of β-xylose reveals a two-fold catalytic itinerary for β-xylanases