Structural basis for ligand recognition in a mushroom lectin: Solvent structure as specificity predictor

GAUTO, D.; DI LELLA, S.; D.A. ESTRIN; MONACO, H.; MARTI, M.A.

CARBOHYDRATE RESEARCH

ELSEVIER SCI LTD

Año: 2011 vol. 346 p. 939 - 948

0008-6215

Lectins are able to recognize specific carbohydrate structures through their carbohydrate recognitiondomain (CRD). The lectin from the mushroom Agaricus bisporus (ABL) has the remarkable ability of selec-tively recognizing the TF-antigen, composed of Galb1-3GalNAc, Ser/Thr linked to proteins, specificallyexposed in neoplastic tissues. Strikingly, the recently solved crystal structure of tetrameric ABL in thepresence of TF-antigen and other carbohydrates showed that each monomer has two CRDs, each beingable to bind specifically to different monosaccharides that differ only in the configuration of a singlehydroxyl, like N-acetyl-D-galactosamine (GalNAc) and N-acetyl-D-glucosamine (GlcNAc). Understandinghow lectin CRDs bind and discriminate mono and/or (poly)-saccharides is an important issue in glycobi-ology, with potential impact in the design of better and selective lectin inhibitors with potential thera-peutic properties. In this work, and based on the unusual monosaccharide epimeric specificity of theABL CRDs, we have performed molecular dynamics simulations of the natural (crystallographic) andinverted (changing GalNAc for GlcNAc and vice-versa) ABL?monosaccharide complexes in order tounderstand the selective ligand recognition properties of each CRD. We also performed a detailed analysisof the CRD local solvent structure, using previously developed methodology, and related it with the rec-ognition mechanism. Our results provide a detailed picture of each ABL CRD specificity, allowing a betterunderstanding of the carbohydrate selective recognition process in this particular lectin.