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The Hidden Conformation of Lewis x, a Human Histo-Blood Group Antigen, Is a Determinant for Recognition by Pathogen Lectins.

Abstract：

:Histo-blood group epitopes are fucosylated branched oligosaccharides with well-defined conformations in solution that are recognized by receptors, such as lectins from pathogens. We report here the results of a series of experimental and computational endeavors revealing the unusual distortion of histo-blood group antigens by bacterial and fungal lectins. The Lewis x trisaccharide adopts a rigid closed conformation in solution, while crystallography and molecular dynamics reveal several higher energy open conformations when bound to the Ralstonia solanacearum lectin, which is in agreement with thermodynamic and kinetic measurements. Extensive molecular dynamics simulations confirm rare transient Le(x) openings in solution, frequently assisted by distortion of the central N-acetyl-glucosamine ring. Additional directed molecular dynamic trajectories revealed the role of a conserved tryptophan residue in guiding the fucose into the binding site. Our findings show that conformational adaptation of oligosaccharides is of paramount importance in cell recognition and should be considered when designing anti-infective glyco-compounds.

journal_name

ACS Chem Biol

journal_title

ACS chemical biology

authors

Topin J,Lelimousin M,Arnaud J,Audfray A,Pérez S,Varrot A,Imberty A

doi

10.1021/acschembio.6b00333

subject

Has Abstract

pub_date

2016-07-15 00:00:00

pages

2011-20

issue

7

eissn

1554-8929

issn

1554-8937

journal_volume

11

pub_type

杂志文章

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