Identifying glycoconjugate-binding domains. Building on the past

The molecular details of how glycoconjugate-binding proteins interact with their ligands have been revealed by a variety of techniques. For example, proteases, chemical-modifying reagents and antibodies have served as effective probes of lectin functional domains. Protein crystallography has providing insight into how lectins are structured, and aided in determining which amino acids in these proteins are positioned appropriately for bond formation with glycoconjugates. In addition, the characterization and sequencing of naturally occurring, non-functional lectin variants have led to the identification of amino acids which play critical roles in a lectin's glycoconjugate-binding domain. Similarly, studies of lectin mutants produced by site-directed mutagenesis, and of synthetic peptides that mimic lectin binding properties, have demonstrated the importance of particular amino acids for glycoconjugate binding. An alternate approach to understanding lectin functional domains has been to compare the primary sequences of these proteins to reveal common sequence elements which allow them to be organized into families. For example, the discovery of amino acid homologies dispersed over long segments of the primary sequences of several lectins has suggested that many of these proteins have a related three-dimensional organization. In addition, the identification of more highly focused regions of sequence homology has indicated that many structures within the lectin glycoconjugate-binding domains themselves may be conserved. Scanning protein data banks for sequences homologous to known lectins has led to the identification of several previously unrecognized lectins, and aided in determining what portions of these proteins function in their glycoconjugate-binding domains.(ABSTRACT TRUNCATED AT 250 WORDS)