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PDBsum entry 1hpl

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protein metals Protein-protein interface(s) links
Hydrolase(carboxylic esterase) PDB id
1hpl
Jmol
Contents
Protein chains
449 a.a. *
Metals
_CA ×2
Waters ×705
* Residue conservation analysis
PDB id:
1hpl
Name: Hydrolase(carboxylic esterase)
Title: Horse pancreatic lipase. The crystal structure at 2.3 angstroms resolution
Structure: Lipase. Chain: a, b. Engineered: yes
Source: Equus caballus. Horse. Organism_taxid: 9796
Resolution:
2.30Å     R-factor:   0.159    
Authors: Y.Bourne,C.Cambillau
Key ref: Y.Bourne et al. (1994). Horse pancreatic lipase. The crystal structure refined at 2.3 A resolution. J Mol Biol, 238, 709-732. PubMed id: 8182745
Date:
27-Jan-93     Release date:   31-May-94    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P29183  (LIPP_HORSE) -  Pancreatic triacylglycerol lipase (Fragment)
Seq:
Struc:
461 a.a.
449 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.3.1.1.3  - Triacylglycerol lipase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Triacylglycerol + H2O = diacylglycerol + a carboxylate
Triacylglycerol
+ H(2)O
= diacylglycerol
+ carboxylate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   1 term 
  Biological process     lipid metabolic process   3 terms 
  Biochemical function     catalytic activity     4 terms  

 

 
    reference    
 
 
J Mol Biol 238:709-732 (1994)
PubMed id: 8182745  
 
 
Horse pancreatic lipase. The crystal structure refined at 2.3 A resolution.
Y.Bourne, C.Martinez, B.Kerfelec, D.Lombardo, C.Chapus, C.Cambillau.
 
  ABSTRACT  
 
Pancreatic lipase (EC 3.1.1.3) plays a key role in dietary fat digestion by converting triacylglycerols into 2-monoacylglycerols and free fatty acids in the intestine. Although the crystallographic structures of the human pancreatic lipase and of a human lipase-porcine colipase complex have been solved, no refined structure of pancreatic lipase has yet been published. The crystal structure of the horse enzyme was solved by the molecular replacement method from the model of the human pancreatic lipase and subsequently refined to 2.3 A resolution. The final model contains two molecules of 449 amino acid residues each in the asymmetric unit, 705 well-defined water molecules and two calcium ions. The two molecules in the asymmetric unit of the orthorhombic crystals are related by a 2-fold non-crystallographic symmetry axis as in the case of the human lipase. However, the association between the two molecules in their respective crystal forms is different. The overall molecular structure of the horse lipase is very similar to that of the human enzyme. The horse lipase is made up of two well-defined domains. The N-terminal domain which bears the active centre has a typical alpha/beta hydrolase fold topology. The C-terminal domain which is devoted to colipase binding has a beta-sheet sandwich topology. Comparison of equivalent C alpha atom positions between the final model of the horse lipase and the human lipase structure shows only slight differences which are mainly located in the C-terminal domain. The horse enzyme possesses the common features of the known mammalian and microbial lipases, in particular the "flap" covering the catalytic triad. In addition to more precise information concerning these features, the elucidation of the horse lipase crystal structure allowed us to better understand the structural basis of the kinetic behaviour of pancreatic lipases towards a soluble substrate, p-nitrophenyl acetate, and the different sensitivity of these enzymes towards limited proteolysis.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21267636 R.S.Holmes, J.L.Vandeberg, and L.A.Cox (2011).
Vertebrate endothelial lipase: comparative studies of an ancient gene and protein in vertebrate evolution.
  Genetica, 139, 291-304.  
20300652 D.E.Almonacid, E.R.Yera, J.B.Mitchell, and P.C.Babbitt (2010).
Quantitative comparison of catalytic mechanisms and overall reactions in convergently evolved enzymes: implications for classification of enzyme function.
  PLoS Comput Biol, 6, e1000700.  
19567873 N.Griffon, W.Jin, T.J.Petty, J.Millar, K.O.Badellino, J.G.Saven, D.H.Marchadier, E.S.Kempner, J.Billheimer, J.M.Glick, and D.J.Rader (2009).
Identification of the active form of endothelial lipase, a homodimer in a head-to-tail conformation.
  J Biol Chem, 284, 23322-23330.  
17961181 A.Berton, C.Sebban-Kreuzer, and I.Crenon (2007).
Role of the structural domains in the functional properties of pancreatic lipase-related protein 2.
  FEBS J, 274, 6011-6023.  
15890938 J.P.Kamil, B.K.Tischer, S.Trapp, V.K.Nair, N.Osterrieder, and H.J.Kung (2005).
vLIP, a viral lipase homologue, is a virulence factor of Marek's disease virus.
  J Virol, 79, 6984-6996.  
12081491 S.Jayne, B.Kerfelec, E.Foglizzo, S.Granon, J.Hermoso, C.Chapus, and I.Crenon (2002).
Activation of horse PLRP2 by bile salts does not require colipase.
  Biochemistry, 41, 8422-8428.  
12230584 Y.Kobayashi, T.Nakajima, and I.Inoue (2002).
Molecular modeling of the dimeric structure of human lipoprotein lipase and functional studies of the carboxyl-terminal domain.
  Eur J Biochem, 269, 4701-4710.  
10660587 D.Pignol, L.Ayvazian, B.Kerfelec, P.Timmins, I.Crenon, J.Hermoso, J.C.Fontecilla-Camps, and C.Chapus (2000).
Critical role of micelles in pancreatic lipase activation revealed by small angle neutron scattering.
  J Biol Chem, 275, 4220-4224.  
10820517 N.Bruneau, D.Lombardo, E.Levy, and M.Bendayan (2000).
Roles of molecular chaperones in pancreatic secretion and their involvement in intestinal absorption.
  Microsc Res Tech, 49, 329-345.  
10570245 H.van Tilbeurgh, S.Bezzine, C.Cambillau, R.Verger, and F.Carrière (1999).
Colipase: structure and interaction with pancreatic lipase.
  Biochim Biophys Acta, 1441, 173-184.  
9837944 L.Ayvazian, I.Crenon, J.Hermoso, D.Pignol, C.Chapus, and B.Kerfelec (1998).
Ion pairing between lipase and colipase plays a critical role in catalysis.
  J Biol Chem, 273, 33604-33609.  
9720253 S.Bezzine, A.Roussel, J.de Caro, L.Gastinel, A.de Caro, F.Carrière, S.Leydier, R.Verger, and C.Cambillau (1998).
An inactive pancreatic lipase-related protein is activated into a triglyceride-lipase by mutagenesis based on the 3-D structure.
  Chem Phys Lipids, 93, 103-114.  
9032074 J.D.Schrag, Y.Li, M.Cygler, D.Lang, T.Burgdorf, H.J.Hecht, R.Schmid, D.Schomburg, T.J.Rydel, J.D.Oliver, L.C.Strickland, C.M.Dunaway, S.B.Larson, J.Day, and A.McPherson (1997).
The open conformation of a Pseudomonas lipase.
  Structure, 5, 187-202.
PDB codes: 2lip 3lip
9032073 K.K.Kim, H.K.Song, D.H.Shin, K.Y.Hwang, and S.W.Suh (1997).
The crystal structure of a triacylglycerol lipase from Pseudomonas cepacia reveals a highly open conformation in the absence of a bound inhibitor.
  Structure, 5, 173-185.
PDB code: 1oil
8555209 A.Nicolas, M.Egmond, C.T.Verrips, J.de Vlieg, S.Longhi, C.Cambillau, and C.Martinez (1996).
Contribution of cutinase serine 42 side chain to the stabilization of the oxyanion transition state.
  Biochemistry, 35, 398-410.
PDB codes: 1ffa 1ffb 1ffc 1ffd 1ffe
8939760 C.Withers-Martinez, F.Carrière, R.Verger, D.Bourgeois, and C.Cambillau (1996).
A pancreatic lipase with a phospholipase A1 activity: crystal structure of a chimeric pancreatic lipase-related protein 2 from guinea pig.
  Structure, 4, 1363-1374.
PDB code: 1gpl
8663362 J.Hermoso, D.Pignol, B.Kerfelec, I.Crenon, C.Chapus, and J.C.Fontecilla-Camps (1996).
Lipase activation by nonionic detergents. The crystal structure of the porcine lipase-colipase-tetraethylene glycol monooctyl ether complex.
  J Biol Chem, 271, 18007-18016.
PDB code: 1eth
8824281 J.Kobayashi, D.Applebaum-Bowden, K.A.Dugi, D.R.Brown, V.S.Kashyap, C.Parrott, C.Duarte, N.Maeda, and S.Santamarina-Fojo (1996).
Analysis of protein structure-function in vivo. Adenovirus-mediated transfer of lipase lid mutants in hepatic lipase-deficient mice.
  J Biol Chem, 271, 26296-26301.  
8718858 W.Minor, J.Steczko, B.Stec, Z.Otwinowski, J.T.Bolin, R.Walter, and B.Axelrod (1996).
Crystal structure of soybean lipoxygenase L-1 at 1.4 A resolution.
  Biochemistry, 35, 10687-10701.
PDB code: 1yge
7592706 K.A.Dugi, H.L.Dichek, and S.Santamarina-Fojo (1995).
Human hepatic and lipoprotein lipase: the loop covering the catalytic site mediates lipase substrate specificity.
  J Biol Chem, 270, 25396-25401.  
7768883 L.Serre, E.C.Verbree, Z.Dauter, A.R.Stuitje, and Z.S.Derewenda (1995).
The Escherichia coli malonyl-CoA:acyl carrier protein transacylase at 1.5-A resolution. Crystal structure of a fatty acid synthase component.
  J Biol Chem, 270, 12961-12964.
PDB code: 1mla
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.