Mannobiose Binding Induces Changes in Hydrogen Bonding and Protonation States of Acidic Residues in Concanavalin A As Revealed by Neutron Crystallography

Oksana O. Gerlits; Leighton Coates; Robert J. Woods; Andrey Kovalevsky

doi:10.1021/acs.biochem.7b00654

Mannobiose Binding Induces Changes in Hydrogen Bonding and Protonation States of Acidic Residues in Concanavalin A As Revealed by Neutron Crystallography

Oksana O. Gerlits, Leighton Coates, Robert J. Woods, Andrey Kovalevsky

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

26 Scopus citations

Abstract

Plant lectins are carbohydrate-binding proteins with various biomedical applications. Concanavalin A (Con A) holds promise in treating cancerous tumors. To better understand the Con A carbohydrate binding specificity, we obtained a roomerature neutron structure of this legume lectin in complex with a disaccharide Manα1-2Man, mannobiose. The neutron structure afforded direct visualization of the hydrogen bonding between the protein and ligand, showing that the ligand is able to alter both protonation states and interactions for residues located close to and distant from the binding site. An unprecedented low-barrier hydrogen bond was observed forming between the carboxylic side chains of Asp28 and Glu8, with the D atom positioned equidistant from the oxygen atoms having an O···D···O angle of 101.5°.

Original language	English
Pages (from-to)	4747-4750
Number of pages	4
Journal	Biochemistry
Volume	56
Issue number	36
DOIs	https://doi.org/10.1021/acs.biochem.7b00654
State	Published - Sep 12 2017

Funding

*E-mail: [email protected]. Phone: +1 505 310 4184. ORCID Andrey Kovalevsky: 0000-0003-4459-9142 Author Contributions O.O.G., L.C., R.J.W., and A.K. designed the research. O.O.G. and A.K. performed the research. O.O.G. analyzed data. O.O.G., L.C., R.J.W., and A.K. wrote the paper. Funding The research at Oak Ridge National Laboratory’s (ORNL’s) Spallation Neutron Source and High Flux Isotope Reactor was sponsored by the Scientific User Facilities Division, Office of Basic Energy Sciences, U.S. Department of Energy (US DOE). The Office of Biological and Environmental Research supported research at ORNL’s Center for Structural Molecular Biology (CSMB), using facilities supported by the Scientific User Facilities Division, Office of Basic Energy Sciences, US DOE. IMAGINE instrument operations are supported by the Office of Basic Energy Sciences, US DOE. This paper has been authored by UT-Battelle LLC under DOE Contract DE-AC05-00OR22725.

Funders	Funder number
ORNL’s
Scientific User Facilities Division
U.S. Department of Energy	DE-AC05-00OR22725
National Institute of General Medical Sciences	P41GM103390
Basic Energy Sciences
Biological and Environmental Research
Oak Ridge National Laboratory
UT-Battelle

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title = "Mannobiose Binding Induces Changes in Hydrogen Bonding and Protonation States of Acidic Residues in Concanavalin A As Revealed by Neutron Crystallography",

abstract = "Plant lectins are carbohydrate-binding proteins with various biomedical applications. Concanavalin A (Con A) holds promise in treating cancerous tumors. To better understand the Con A carbohydrate binding specificity, we obtained a roomerature neutron structure of this legume lectin in complex with a disaccharide Manα1-2Man, mannobiose. The neutron structure afforded direct visualization of the hydrogen bonding between the protein and ligand, showing that the ligand is able to alter both protonation states and interactions for residues located close to and distant from the binding site. An unprecedented low-barrier hydrogen bond was observed forming between the carboxylic side chains of Asp28 and Glu8, with the D atom positioned equidistant from the oxygen atoms having an O···D···O angle of 101.5°.",

author = "Gerlits, {Oksana O.} and Leighton Coates and Woods, {Robert J.} and Andrey Kovalevsky",

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T1 - Mannobiose Binding Induces Changes in Hydrogen Bonding and Protonation States of Acidic Residues in Concanavalin A As Revealed by Neutron Crystallography

AU - Gerlits, Oksana O.

AU - Coates, Leighton

AU - Woods, Robert J.

AU - Kovalevsky, Andrey

PY - 2017/9/12

Y1 - 2017/9/12

N2 - Plant lectins are carbohydrate-binding proteins with various biomedical applications. Concanavalin A (Con A) holds promise in treating cancerous tumors. To better understand the Con A carbohydrate binding specificity, we obtained a roomerature neutron structure of this legume lectin in complex with a disaccharide Manα1-2Man, mannobiose. The neutron structure afforded direct visualization of the hydrogen bonding between the protein and ligand, showing that the ligand is able to alter both protonation states and interactions for residues located close to and distant from the binding site. An unprecedented low-barrier hydrogen bond was observed forming between the carboxylic side chains of Asp28 and Glu8, with the D atom positioned equidistant from the oxygen atoms having an O···D···O angle of 101.5°.

AB - Plant lectins are carbohydrate-binding proteins with various biomedical applications. Concanavalin A (Con A) holds promise in treating cancerous tumors. To better understand the Con A carbohydrate binding specificity, we obtained a roomerature neutron structure of this legume lectin in complex with a disaccharide Manα1-2Man, mannobiose. The neutron structure afforded direct visualization of the hydrogen bonding between the protein and ligand, showing that the ligand is able to alter both protonation states and interactions for residues located close to and distant from the binding site. An unprecedented low-barrier hydrogen bond was observed forming between the carboxylic side chains of Asp28 and Glu8, with the D atom positioned equidistant from the oxygen atoms having an O···D···O angle of 101.5°.

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Mannobiose Binding Induces Changes in Hydrogen Bonding and Protonation States of Acidic Residues in Concanavalin A As Revealed by Neutron Crystallography

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