title: The role of lysyl residues of phospholipases A2 in the formation of the catalytic complex.
abstract: The aspartyl residue at position 49 in phospholipases A2 (PLA) has been viewed as a component of the catalytic apparatus because of its involvement in binding the essential cofactor, calcium. We recently discovered a new class of PLA's in which, among other changes in highly invariant residues, Asp-49 is replaced by a lysine (Maraganore et al. (1984) J. Biol. Chem. 259, 13839). These Lys-49 PLA's are also calcium-dependent, but, in contrast to the Asp-49 enzymes, they bind phospholipid strongly in the absence of calcium. Lys-49 PLA's are, therefore, ideal for studying structural and mechanistic aspects of these enzymes. Attempts to modify Lys-49 with the amino group-specific reagent, trinitrobenzenesulfonic acid (TNBS) led to the inactivation of the PLA, but reaction occurred not as expected at position 49, but at Lys-53. These findings lead us to propose a model, applicable to PLA's in general, in which cationic side chains at position 53 in these enzymes participate in phospholipid binding on the path to formation of the catalytic complex. This model serves to explain a number of unresolved observations in the current literature relating to enzyme-substrate interactions in the PLA's.
mesh_terms: D000818:Animals; D001224:Aspartic Acid; D002118:Calcium / Q000494:pharmacology; D055598:Chemical Phenomena; D002621:Chemistry; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008239:Lysine; D010446:Peptide Fragments / Q000378:metabolism; D010740:Phospholipases / Q000378:metabolism*; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012911:Snakes / Q000378:metabolism; D013329:Structure-Activity Relationship; D014302:Trinitrobenzenesulfonic Acid / Q000494:pharmacology; D014357:Trypsin / Q000378:metabolism
chemical_list: D010446:Peptide Fragments; D001224:Aspartic Acid; D014302:Trinitrobenzenesulfonic Acid; D010740:Phospholipases; D010741:Phospholipases A; D014357:Trypsin; D008239:Lysine; D002118:Calcium