PMID- 10358049
OWN - NLM
STAT- MEDLINE
DCOM- 19990706
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 24
DP  - 1999 Jun 11
TI  - Crystal structure of human gastric lipase and model of lysosomal acid lipase, two
      lipolytic enzymes of medical interest.
PG  - 16995-7002
AB  - Fat digestion in humans requires not only the classical pancreatic lipase but
      also gastric lipase, which is stable and active despite the highly acidic stomach
      environment. We report here the structure of recombinant human gastric lipase at 
      3.0-A resolution, the first structure to be described within the mammalian acid
      lipase family. This globular enzyme (379 residues) consists of a core domain
      belonging to the alpha/beta hydrolase-fold family and a "cap" domain, which is
      analogous to that present in serine carboxypeptidases. It possesses a classical
      catalytic triad (Ser-153, His-353, Asp-324) and an oxyanion hole (NH groups of
      Gln-154 and Leu-67). Four N-glycosylation sites were identified on the electron
      density maps. The catalytic serine is deeply buried under a segment consisting of
      30 residues, which can be defined as a lid and belonging to the cap domain. The
      displacement of the lid is necessary for the substrates to have access to
      Ser-153. A phosphonate inhibitor was positioned in the active site that clearly
      suggests the location of the hydrophobic substrate binding site. The lysosomal
      acid lipase was modeled by homology, and possible explanations for some
      previously reported mutations leading to the cholesterol ester storage disease
      are given based on the present model.
FAU - Roussel, A
AU  - Roussel A
AD  - Architecture et Fonction des Macromolecules Biologiques, CNRS-IFR1 UPR 9039, 31
      chemin Joseph Aiguier, 13402 Marseille cedex 20, France.
FAU - Canaan, S
AU  - Canaan S
FAU - Egloff, M P
AU  - Egloff MP
FAU - Riviere, M
AU  - Riviere M
FAU - Dupuis, L
AU  - Dupuis L
FAU - Verger, R
AU  - Verger R
FAU - Cambillau, C
AU  - Cambillau C
LA  - eng
SI  - PDB/1HLG
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Organophosphonates)
RN  - 0 (Recombinant Proteins)
RN  - EC 3.1.1.3 (Lipase)
RN  - EC 3.4.- (Carboxypeptidases)
RN  - EC 3.4.16.5 (CTSA protein, human)
RN  - EC 3.4.16.5 (Cathepsin A)
SB  - IM
MH  - Amino Acid Sequence
MH  - Carboxypeptidases/chemistry
MH  - Catalytic Domain
MH  - Cathepsin A
MH  - Computer Simulation
MH  - Crystallography, X-Ray
MH  - Humans
MH  - Lipase/antagonists & inhibitors/*chemistry/genetics
MH  - Lipolysis
MH  - Lysosomes/*enzymology
MH  - Models, Molecular
MH  - Molecular Sequence Data
MH  - Organophosphonates/pharmacology
MH  - Recombinant Proteins/chemistry
MH  - Sequence Homology, Amino Acid
MH  - Stomach/*enzymology
EDAT- 1999/06/08 00:00
MHDA- 1999/06/08 00:01
CRDT- 1999/06/08 00:00
PHST- 1999/06/08 00:00 [pubmed]
PHST- 1999/06/08 00:01 [medline]
PHST- 1999/06/08 00:00 [entrez]
AID - 10.1074/jbc.274.24.16995 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Jun 11;274(24):16995-7002. doi: 10.1074/jbc.274.24.16995.