Issue 21, 2012

Conformational mapping and energetics of saccharide–aromatic residue interactions: implications for the discrimination of anomers and epimers and in protein engineering

Abstract

Aromatic residues play a key role in saccharide-binding sites. Experimental studies have given an estimate of the energetics of saccharide–aromatic residue interactions. In this study, dependence of the energetics on the mutual position-orientation (PO) of saccharide and aromatic residue has been investigated by geometry optimization of a very large number (164) of complexes at MP2/6-31G(d,p) level of theory. The complexes are of Tyr and Phe analogs with α/β-D-Glc, β-D-Gal, α-D-Man and α/β-L-Fuc. A number of iso-energy POs are found for the complexes of all six saccharides. Stacking and non-stacking modes of binding are found to be of comparable strengths. In general, complexes of p-OHTol are stronger than those of Tol, and those dominated by OH⋯O interactions are more stable than ones dominated by CH⋯π interactions. The strengths of OH⋯O/π interactions, but not those of CH⋯π, show large variations. Even though an aromatic residue has a large variety of POs to interact with a saccharide, distinct preferences are found due to anomeric and epimeric differences. An aromatic residue can interact from either the a- or b-face of Glc, but only through the b-face with Gal, its C4-epimer. In contrast, stacking interaction with Man (C2-epimer of Glc) requires the participation of the –CH2OH group and free rotation of this group, as is observed in solution, precludes all modes of stacking interactions. It is also found that an aromatic residue can be strategically placed either to discriminate or to accommodate (i) anomers of Glc and of Fuc and (ii) Gal/Fuc. Thus, analysis of the optimized geometries of by far the largest number of complexes, and with six different saccharides, at this level of theory has given insights into how Nature cleverly uses aromatic residues to fine tune saccharide specificities of proteins. These are of immense utility for protein engineering and protein design studies.

Graphical abstract: Conformational mapping and energetics of saccharide–aromatic residue interactions: implications for the discrimination of anomers and epimers and in protein engineering

Supplementary files

Article information

Article type
Paper
Submitted
24 Jan 2012
Accepted
22 Mar 2012
First published
23 Mar 2012

Org. Biomol. Chem., 2012,10, 4186-4200

Conformational mapping and energetics of saccharide–aromatic residue interactions: implications for the discrimination of anomers and epimers and in protein engineering

M. Kumari, R. B. Sunoj and P. V. Balaji, Org. Biomol. Chem., 2012, 10, 4186 DOI: 10.1039/C2OB25182E

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements