Man α1-2 Man α-OMe-concanavalin A complex reveals a balance of forces involved in carbohydrate recognition

Moothoo, Davina N., Canan, Booma, Field, Robert A. ORCID: https://orcid.org/0000-0001-8574-0275 and Naismith, James H. (1999) Man α1-2 Man α-OMe-concanavalin A complex reveals a balance of forces involved in carbohydrate recognition. Glycobiology, 9 (6). pp. 539-545. ISSN 0959-6658

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Abstract

We have determined the crystal structure of the methyl glycoside of Man α1-2 Man in complex with the carbohydrate binding legume lectin concanavalin A (Con A). Man α1-2 Man α-OMe binds more tightly to concanavalin A than do its α1-3 and α1-6 linked counterparts. There has been much speculation as to why this is so, including a suggestion of the presence of multiple binding sites for the α1-2 linked disaccharide. Crystals of the Man α1-2 Man α-OMe-Con A complex form in the space group P212121 with cell dimensions a = 119.7 Å, b = 119.7 Å, c = 68.9 Å and diffract to 2.75Å. The final model has good geometry and an R factor of 19.6% (R(free) = 22.8%). One tetramer is present in the asymmetric unit. In three of the four subunits, electron density for the disaccharide is visible. In the fourth only a monosaccharide is seen. In one subunit the reducing terminal sugar is recognized by the monosaccharide site; the nonreducing terminal sugar occupies a new site and the major solution conformation of the inter-sugar glycosidic linkage conformation is adopted. In contrast, in another subunit the non reducing terminal sugar sits in the so called monosaccharide binding site; the reducing terminal sugar adopts a different conformation about its inter-sugar glycosidic linkage in order for the methyl group to access a hydrophobic pocket. In the third subunit, electron density for both binding modes is observed. We demonstrate that an extended carbohydrate binding site is capable of binding the disaccharide in two distinct ways. These results provide an insight in to the balance of forces controlling protein carbohydrate interactions.

Item Type: Article
Additional Information: Funding Information: We are grateful to Steve Homans, John Helliwell, and Patrick Wright for discussions, encouragement and advice. We thanks the referees for helpful comments. The research is supported by B.B.S.R.C. Project Grant B08307 (J.H.N.), Glaxo-Wellcome and a B.B.S.R.C. ROPA award (R.A.F.).
Uncontrolled Keywords: carbohydrate conformation,con a saccharide complex,crystal structure,molecular recognition,medicine(all) ,/dk/atira/pure/subjectarea/asjc/2700
Faculty \ School: Faculty of Science > School of Chemistry, Pharmacy and Pharmacology
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Depositing User: LivePure Connector
Date Deposited: 11 Sep 2024 09:30
Last Modified: 25 Sep 2024 18:08
URI: https://ueaeprints.uea.ac.uk/id/eprint/96694
DOI: 10.1093/glycob/9.6.539

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