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 properties: (1) they are activated by lipid/water interfaces (interfacial activation), (2) they are inhibited by bile salts but reactivated by colipase (a small activator protein), and (3) they do not hydrolyze significantly phospholipids. A cDNA clone encoding a guinea pig pancreatic (phospho)lipase (GPL) has been sequenced and expressed. The enzyme (recombinant as well as native) differs from other pancreatic lipases in that (1) it is not interfacially activated, (2) its activity is unaffected by the presence of bile salts and/or colipase using tributyrin as substrate, and (3) it exhibits equally phospholipase A1 and lipase activities. 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 responsible for the anomalous behavior of this enzyme. Thus GPL challenges the classical distinction between lipases, esterases, and phospholipases.
Hjorth
A
A
Novo Nordisk A/S, Copenhagen, Denmark.
Carrière
F
F
Cudrey
C
C
Wöldike
H
H
Boel
E
E
Lawson
D M
DM
Ferrato
F
F
Cambillau
C
C
Dodson
G G
GG
Thim
L
L
D000595:Amino Acid Sequence; D000818:Animals; D001236:Aspergillus oryzae / Q000235:genetics; D001483:Base Sequence; D003001:Cloning, Molecular; D004285:Dogs; D004789:Enzyme Activation; D006168:Guinea Pigs; D008049:Lipase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010179:Pancreas / Q000201:enzymology; D010189:Pancreatic Juice / Q000201:enzymology; D010741:Phospholipases A / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D054466:Phospholipases A1; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship
D011994:Recombinant Proteins; D008049:Lipase; D010741:Phospholipases A; D054466:Phospholipases A1