A STRUCTURAL DOMAIN (THE LID) FOUND IN PANCREATIC LIPASES IS ABSENT IN THE GUINEA-PIG (PHOSPHO)LIPASE

Typically pancreatic lipases are characterized by the following proper ties: (1) they are activated by lipid/water interfaces (interfacial ac tivation), (2) they are inhibited by bile salts but reactivated by col ipase (a small activator protein), and (3) they do not hydrolyze signi ficantly phospholipids. A cDNA clone encoding a guinea pig pancreatic (phospho)lipase (GPL) has been sequenced and expressed. The enzyme (re combinant as well as native) differs from other pancreatic lipases in that (1) it is not interfacially activated, (2) its activity is unaffe cted by the presence of bile salts and/or colipase using tributyrin as substrate, and (3) it exhibits equally phospholipase A1 and lipase ac tivities. The amino acid sequence of GPL is highly homologous to that of other known pancreatic lipases, with the exception of a deletion in the so-called lid domain that regulates access to the active centers of other lipases. We propose that this deletion is directly responsibl e for the anomalous behavior of this enzyme. Thus GPL challenges the c lassical distinction between lipases, esterases, and phospholipases.