Stereochemical metrics of lectin-carbohydrate interactions: comparison with protein-protein interfaces

Abstract

A global census of stereochemical metrics including interface size, hydropathy, amino acid propensities, packing and hydrogen bonding was carried out on 32 x-ray-elucidated structures of lectin-carbohydrate complexes covering eight different lectin families. It is shown that the interactions at primary binding subsites are more efficient than at other subsites. Another salient behavior found for primary subsites was a marked negative correlation between the interface size and the polar surface content. It is noteworthy that this demographic rule is delineated by lectins with unrelated phylogenetic origin, indicating that independent interface architectures have evolved through common optimization paths. The structural properties of lectin-carbohydrate interfaces were compared with those characterizing a set of 32 protein homodimers. Overall, the analysis shows that the stereochemical bases of lectin-carbohydrate and protein-protein interfaces differ drastically from each other. In comparison with protein-protein complexes, lectin-carbohydrate interfaces have superior packing efficiency, better hydrogen bonding stereochemistry, and higher interaction cooperativity. A similar conclusion holds in the comparison with protein-protein heterocomplexes. We propose that the energetic consequence of this better interaction geometry is a larger decrease in free energy per unit of area buried, feature that enables lectins and carbohydrates to form stable complexes with relatively small interface areas. These observations lend support to the emerging notion that systems differing from each other in their stereochemical metrics may rely on different energetic bases.

Structural and biochemical studies of the C-terminal domain of mouse peptide-N-glycanase identify it as a mannose-binding module

“…The types of residues located in this putative binding pocket are entirely consistent with those commonly observed in carbohydrate binding (18,19). In addition to having structural similarities, the two proteins also share biochemical properties.…”

Binding Thermodynamics of Phosphorylated Inhibitors to Triosephosphate Isomerase and the Contribution of Electrostatic Interactions

“…In P-C systems, the contribution of polar areas was more highly weighted than in other models, which seems to be due to stronger and more abundant hydrogen bonds at the interface of P-C complexes compared to P-P interfaces. 48 In this work, the P-C model, as a whole, yields values more similar to experimental ΔH b (at 25°C and 0.06 M ionic strength): -48.0 kJ mol -1 for TIM-2PG (ΔH b,exp = -40.8 kJ mol -1 ) and -55.1 kJ mol -1 for TIM-PGH (ΔH b,exp = -60.0 kJ mol -1 ). The two other models, P-P and P-L, underestimate the exothermic ΔH b , and their predictions are more similar to the experimental values obtained at high ionic strength.…”

Carbohydrate Recognition and Signaling

“…The structural and thermodynamic basis for this specificity has, in fact, been well studied and reviewed in detail elsewhere [17][18][19][20][21][22][23]. From a structural standpoint, this is achieved by a complementarity of fit between the CRD and the saccharide moiety which includes both hydrogen bond and van der Waals interactions.…”