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

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Title Conformational mapping and energetics of saccharide-aromatic residue interactions: implications for the discrimination of anomers and epimers and in protein engineering
 
Creator KUMARI, M
SUNOJ, RB
BALAJI, PV
 
Subject AB-INITIO CALCULATIONS
MOLECULAR RECOGNITION
HYDROGEN-BONDS
BINDING-SITES
CARBOHYDRATE-BINDING
STRUCTURAL FEATURES
CRYSTAL-STRUCTURE
ANALOG COMPLEXES
PI INTERACTIONS
NMR
 
Description 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 alpha/beta-D-Glc, beta-D-Gal, alpha-D-Man and alpha/beta-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 center dot center dot center dot O interactions are more stable than ones dominated by CH center dot center dot center dot pi interactions. The strengths of OH center dot center dot center dot O/pi interactions, but not those of CH center dot center dot center dot pi, 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.
 
Publisher ROYAL SOC CHEMISTRY
 
Date 2014-10-16T05:30:35Z
2014-10-16T05:30:35Z
2012
 
Type Article
 
Identifier ORGANIC & BIOMOLECULAR CHEMISTRY, 10(21)4186-4200
http://dx.doi.org/10.1039/c2ob25182e
http://dspace.library.iitb.ac.in/jspui/handle/100/15341
 
Language en