Structural studies on peanut lectin complexed with disaccharides involving different linkages: further insights into the structure and interactions of the lectin

Abstract

Crystal structures of peanut lectin complexed with Galbeta1-3Gal, methyl-T-antigen, Galbeta1-6GalNAc, Galalpha1-3Gal and Galalpha1-6Glc and that of a crystal grown in the presence of Galalpha1-3Galbeta1-4Gal have been determined using data collected at 100 K. The use of water bridges as a strategy for generating carbohydrate specificity was previously deduced from the complexes of the lectin with lactose (Galbeta1-4Glc) and T-antigen (Galbeta1-3GalNAc). This has been confirmed by the analysis of the complexes with Galbeta1-3Gal and methyl-T-antigen (Galbeta1-3GalNAc-alpha-OMe). A detailed analysis of lectin-sugar interactions in the complexes shows that they are more extensive when the beta-anomer is involved in the linkage. As expected, the second sugar residue is ill-defined when the linkage is 1-->6. There are more than two dozen water molecules which occur in the hydration shells of all structures determined at resolutions better than 2.5 A. Most of them are involved in stabilizing the structure, particularly loops. Water molecules involved in lectin-sugar interactions are also substantially conserved. The lectin molecule is fairly rigid and does not appear to be affected by changes in temperature.

Crystal Structures of the Transcriptional Repressor RolR Reveals a Novel Recognition Mechanism between Inducer and Regulator

“…For example, it is recently reported that the antitumor galectin AAL recognizes its bioactive ligand, the TF antigen, by using a Glu-Water-Arg-Water motif [15]. The peanut lectin employs the water bridges for generating carbohydrate specificity [16]. Diego et al, also reported that water molecules on the surface of the carbohydrate recognition domain of galectins were related to the galectins' affinity for carbohydrate ligand recognition [17].…”

Structural insights into the recognition mechanism between an antitumor galectin AAL and the Thomsen‐Friedenreich antigen

“…In fact, lectins using water molecules to recognize the carbohydrate is frequently observed. For example, the peanut lectin employs the water bridges for generating carbohydrate specificity (26). Diego et al .…”

“…In fact, lectins using water molecules to recognize the carbohydrate is frequently observed. For example, the peanut lectin employs the water bridges for generating carbohydrate specificity (26). Diego et al (27) also reported that water molecules on the surface of the carbohydrate recognition domain of galectins were related to the galectins' affinity for carbohydrate ligand recognition.…”

Structural diversity and ligand specificity of lectins. The Bangalore effort

“…The three two-fold axes combine to give rise to an irrational screw axis, Q, perpendicular to all of them and relates C to A (146°, 24 Å) and D to B (-146°, -24 Å). Repeated occurrence of the same quaternary structure in crystal forms of the lectin grown under widely different conditions [17][18][19][20][21][22][23][24] demonstrates that the observed open conformation is not an artefact of crystallization. Solution studies also showed that PNA is a tetramer and that the tetrameric association in it is perhaps stronger than that in well known tetrameric proteins like ConA and hemoglobin.…”

“…PNA-sugar interactions have been investigated through the X-ray analysis of a number complexes with carbohydrates including a number of disaccharides with different glycosidic linkages between the monosaccharide residues [17][18][19][20][21][22][23]. The interactions involve four binding loops, residues 75-83, 91-106, 125-135 and 211-216 in all of them.…”