First crystallized by Sumner and Howell (1936), Concanavalin A (ConA) has proven to be an interesting and useful lectin. Lectins are proteins that react with specific terminal sugar residues and are useful probes in studying carbohydrates of cell surfaces. See review by Sharon and Lis (1972). The properties of ConA have been extensively dealt with in the published proceedings of an International Symposium on ConA (Concanavalin A, T.K. Chowdhury and A.K. Weiss, eds., Plenum Press, New York, 1975).
Characteristics of Concanavalin A from Jack Bean:
The molecular structure of ConA has been reported by Becker et al. (1976), Becker et al. (1975), Cunningham et al. (1975), Reeke et al. (1975) and Wang et al. (1975). It is composed of identical subunits of 237 amino acid residues (M.W.: 26,000) with no covalently bound carbohydrate or other prosthetic group. Olson and Liener (1967) report no cystine residues. See also Edmondson et al. (1971). According to McKenzie et al. (1972), at pH 4.5-5.6 (I=0.1), ConA exists as a single dimer (M.W.: 53,000). Above pH 7 it is predominantly tetrameric (Wang et al. 1975). Its optimal activity is near pH 7.
ConA binds two metal ions per monomer: a transition metal, nominally Mn2+ (See Becker et al. 1975) at site S1 and Ca2+ at S2. Both must be present for saccharide binding. (Grimaldi and Sykes 1975; Jack et al. 1971; Poretz and Goldstein 1970; Greer et al. 1970; Agrawal et al. 1968; Goldstein et al. 1965). See also Barber and Carver (1975) and Barber et al. (1975). The transitional metal site has been reported on by Sherry et al. (1975).
ConA reacts with non-reducing α-D-glucose and α-D-mannose - it is the ring form that participates in the reaction. Smith and Goldstein (1967) report on the stereochemical requirements of the active sites. α-methyl-D-glucopyranoside acts as a competitive inhibitor. Goldstein et al. (1965) report on simple sugar inhibition and indicate unmodified OH groups at C-3, C-4 and C-6 are essential for binding.
Magnetic resonance studies have been reported by Barber et al. (1975) and Grimaldi and Sykes (1975). Luminescent properties are similar to other tyrosine and tryptophane containing proteins (Miller and Nwokedi 1975). Beppu et al. (1975) report on labelled ConA.
As indicated above, the usefulness of ConA lies in its specific binding action with certain carbohydrate-containing receptors. It agglutinates red blood cells and complexes with blood group substances (Clark and Denborough 1971) and immunoglobulin glycopeptides (Kornfeld and Ferris 1975) and carcinoembryonic antigens (Brattain et al. 1975; Boenisch and Norgaard-Pedersen 1975). See also Pitlick (1975). Harmony and Cordes (1975) report on its interaction with human plasma low density lipoprotein.
ConA exhibits mitogenic activity with lymphocytes (Ruscetti and Chervenick 1975; Novogrodsky and Katchalski 1971; Perlmann et al. 1970). Bessler and Lipps (1976) report its effect on protozoan nucleus.
Cancer cells are readily aggregated by ConA; normal cells are not (Shoham et al. 1970; Inbar and Sachs 1969). See also Ben-Bassat and Goldblum (1975) and Kolata (1975). Moscona (1971) reports that embryonic cells are also aggregatable. Normal cells react after proteolytic treatment. Nicholson (1972) suggests that trypsinization causes clustering of the membrane ConA sites. On the other hand, Burger and Noonan (1970) report that ConA treated with trypsin can restore growth patterns of transformed fibroblasts to normal.
Studies of ConA with particular cell types include locust muscle fibers, Mathers and Usherwood (1976); lymphocytes, Ben-Bassat and Goldblum (1975), Beyer and Bowers (1975), DePetris (1975), Pommier et al. (1975); fibroblasts, Huet and Bernadac (1975); adipocytes, Katzen and Soderman (1975); rat liver plasma membrane components, Berzins and Blomberg (1975). Sutou and Shindo (1975) report that ConA induces endoreduplication in mammalian cells and Kubota and Kanatani (1975) indicate that it induces oocyte maturation-inducing substance in starfish follicle cells. ConA reaction with E. coli has been reported by Picken and Beachman (1975); that with Dictyostelium discoideum by Weeks (1975); and that with B. substilis by Birdsell and Doyle (1973). Brunson and Watson (1975) report on activity with lipopolysaccharide.
Immobilized specific lectins are useful for purifying glycoprotein (Avrameas and Guilbert 1971; Allan et al. 1972; and Anderson and Lee-Own 1974) and removing contaminants, (Edelman 1975). Wood and Sarinana (1975) report on use of ConA in studying nerve glycoproteins.