A. Hjorth et al., A STRUCTURAL DOMAIN (THE LID) FOUND IN PANCREATIC LIPASES IS ABSENT IN THE GUINEA-PIG (PHOSPHO)LIPASE, Biochemistry, 32(18), 1993, pp. 4702-4707
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.