← Back to Search
Structure Of Human Pancreatic Lipase
F. Winkler, A. D'arcy, W. Hunziker
Published 1990 · Biology, Medicine
Download PDFAnalyze on Scholarcy
PANCREATIC lipase (triacylglycerol acyl hydrolase) fulfills a key function in dietary fat absorption by hydrolysing triglycerides into diglycerides and subsequently into monoglycerides and free fatty acids. We have determined the three-dimensional structure of the human enzyme, a single-chain glycoprotein of 449 amino acids, by X-ray crystallography and established its primary structure by sequencing complementary DNA clones. Enzymatic activity is lost after chemical modification of Ser 152 in the porcine enzyme1,2, indicating that this residue is essential in catalysis, but other data3,4 are more consistent with a function in interfacial recogni-tion. Our structural results are evidence that Ser 152 is the nucleophilic residue essential for catalysis. It is located in the larger N-terminal domain at the C-terminal edge of a doubly wound parallel β-sheet and is part of an Asp-His-Ser triad, which is chemically analogous to, but structurally different from, that in the serine proteases. This putative hydrolytic site is covered by a surface loop and is therefore inaccessible to solvent. Interfacial activation, a characteristic property of lipolytic enzymes acting on water-insoluble substrates at water-lipid interfaces, probably involves a reorientation of this flap, not only in pancreatic lipases but also in the homologous hepatic and lipoprotein lipases.
This paper references
Boronic acid inhibitors of porcine pancreatic lipase.
C. W. Garner (1980)
A graphics model building and refinement system for macromolecules
T. Jones (1978)
Hydrolysis of p-nitrophenyl acetate by the peptide chain fragment (336-449) of porcine pancreatic lipase.
J. De Caro (1986)
Porcine pancreatic lipase. Completion of the primary structure.
J. De Caro (1981)
Describing patterns of protein tertiary structure.
J. Richardson (1985)
Crystallographic R Factor Refinement by Molecular Dynamics
Axel T. BR�NGER (1987)
Handedness of crossover connections in beta sheets.
J. Richardson (1976)
The refined crystal structure of bovine beta-trypsin at 1.8 A resolution. II. Crystallographic refinement, calcium binding site, benzamidine binding site and active site at pH 7.0.
W. Bode (1975)
Minireview on pancreatic lipase and colipase.
C. Chapus (1988)
Methods and programs for direct‐space exploitation of geometric redundancies
G. Bricogne (1976)
Characterization of the serine reacting with diethyl p-nitrophenyl phosphate in porcine pancreatic lipase.
A. Guidoni (1981)
Structural features of lipoprotein lipase
B. Persson (1989)
Evaluation of Single-Crystal X-ray Diffraction Data from a Position-Sensitive Detector
W. Kabsch (1988)
Mechanism of pancreatic lipase action. 1. Interfacial activation of pancreatic lipase.
C. Chapus (1976)
Human hepatic lipase. Cloned cDNA sequence, restriction fragment length polymorphisms, chromosomal localization, and evolutionary relationships with lipoprotein lipase and pancreatic lipase.
S. Datta (1988)
Lipoprotein lipase: modification of its kinetic properties by mild tryptic digestion.
G. Bengtsson (1981)
On the conformation of proteins: the handedness of the connection between parallel beta-strands.
M. Sternberg (1977)
Action of organophosphates and sulfonyl halides on porcine pancreatic lipase.
M. F. Maylié (1972)
Primary Structures of Canine Pancreatic Lipase and Phospholipase A2 Messenger RNAs
B. Kerfelec (1986)
Mechanism of pancreatic lipase action. 2. Catalytic properties of modified lipases.
C. Chapus (1976)
A least‐squares refinement method for isomorphous replacement
R. E. Dickerson (1968)
Dictionary of protein secondary structure: Pattern recognition of hydrogen‐bonded and geometrical features
W. Kabsch (1983)
Lipoprotein lipases from cow, guinea-pig and man. Structural characterization and identification of protease-sensitive internal regions.
G. Bengtsson-Olivecrona (1986)
The Protein Data Bank. A computer-based archival file for macromolecular structures.
F. Bernstein (1977)
This paper is referenced by
Thermophilic Moulds in Biotechnology
B. Johri (1999)
A single glycine-rich repeat of Pseudomonas chlororaphis Polyurethanase A mediates secretion of a GST fusion protein in Escherichia coli
P. Langlois (2002)
Expression and characterization of Geotrichum candidum lipase I gene. Comparison of specificity profile with lipase II.
M. Bertolini (1995)
Fatty acid selectivity of a lipase purified from Vernonia galamensis seed.
I. Ncube (1995)
Biodegradation of lipids by wood sapstaining OPHIOSTOMA SPP
Y. Gao (1996)
Digestion in the newborn.
M. Hamosh (1996)
Exocrine Disorders of the Pancreas
F. V. Lente (1997)
Direct Activation of Human Phospholipase C by Its Well Known Inhibitor U73122*
Ryan R. Klein (2011)
Microbial lipases form versatile tools for biotechnology.
K. E. Jaeger (1998)
Overexpression and protein engineering of lipase A and B from Geotrichum candidum CMICC335426
E. Catoni (1999)
Ion Pairing between Lipase and Colipase Plays a Critical Role in Catalysis*
L. Ayvazian (1998)
Chapter 5 - Enzymatic Reactions at Interfaces
Ropers Marie-Hélène (2002)
Synthesis of lipophilic aldehydes and study of their inhibition effect on human digestive lipases.
S. Kotsovolou (2002)
Expression of Rhizopus oryzae lipase gene in Saccharomyces cerevisiae
M. Ueda (2002)
In vitro and in vivo degradation studies for development of a biodegradable patch based on poly(3-hydroxybutyrate).
T. Freier (2002)
A Novel Phosphatidic Acid-selective Phospholipase A1That Produces Lysophosphatidic Acid*
H. Sonoda (2002)
Molecules of Interest Serine carboxypeptidase-like acyltransferases
C. Milkowski (2004)
Lipase-catalyzed Approaches towards Secondary Alcohols: Intermediates for Enantiopure Drugs
Mihaela C. Turcu (2010)
The β9 loop domain of PA-PLA1α has a crucial role in autosomal recessive woolly hair/hypotrichosis.
S. Shinkuma (2012)
Megaporous poly(hydroxy ethylmethacrylate) based poly(glycidylmethacrylate-N-methacryloly-(L)-tryptophan) embedded composite cryogel.
Deniz Türkmen (2015)
mRNA encoding a new lipolytic enzyme expressed in rabbit lacrimal glands.
S. G. Remington (2002)
Hydrolases Enzymes Functionally Related to Serine Hydrolase-Fold Superfamily of β / α of the Bacterial 2 , 4-Dioxygenases : New Members
F. Fischer (1999)
Lipoprotein lipase is active as a monomer
A. Beigneux (2019)
Effects of aging on fat deposition and meat quality in Sheldrake duck
J. He (2018)
Pancreatic Enzymes in Health and Disease
P. G. Lankisch (1991)
Molecular Dynamics Simulation of Human Pancreatic Lipase and Lipase-colipase Complex: Insight into the Structural Fluctuations and Conformational Changes
S. A. Ahmed (2020)
Investigating the role of phosphorylation in the regulation of Diacylglycerol Lipase α/β activity
Praveen M. Singh (2013)
Purification, biochemical and molecular study of lipase producing from a newly thermoalkaliphilic Aeribacillus pallidus for oily wastewater treatment.
A. Ktata (2019)
Proteolytic activity and reverse genetics phenotype of EAV nsp4 protease mutants carrying replacements of residues Arg-4, Asp-119, and Arg-203
D. V. Aken (2008)
Dromedary pancreatic lipase: purification and structural properties.
H. Mejdoub (1994)
Growth-phase-dependent expression of the lipolytic system of Acinetobacter calcoaceticus BD413: cloning of a gene encoding one of the esterases.
R. Kok (1993)
Biocatalytic resolution of DL-propranolol. A successful example of computer-aided substrate design
Ching‐Shih Chen (1993)See more