spacer
spacer

PDBsum entry 2lip

Go to PDB code: 
protein metals links
Hydrolase PDB id
2lip
Jmol
Contents
Protein chain
320 a.a. *
Metals
_CA
Waters ×91
* Residue conservation analysis
PDB id:
2lip
Name: Hydrolase
Title: Pseudomonas lipase open conformation
Structure: Lipase. Chain: a. Synonym: triacylglycerol hydrolase. Ec: 3.1.1.3
Source: Burkholderia cepacia. Organism_taxid: 292. Other_details: commercial prep from genzyme corporation
Resolution:
2.10Å     R-factor:   0.163     R-free:   0.220
Authors: J.D.Schrag,M.Cygler
Key ref:
J.D.Schrag et al. (1997). The open conformation of a Pseudomonas lipase. Structure, 5, 187-202. PubMed id: 9032074 DOI: 10.1016/S0969-2126(97)00178-0
Date:
13-Dec-96     Release date:   12-Mar-97    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P22088  (LIP_BURCE) -  Lipase
Seq:
Struc:
364 a.a.
320 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 18 residue positions (black crosses)

 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!
  Biological process     lipid metabolic process   2 terms 
  Biochemical function     hydrolase activity     3 terms  

 

 
    reference    
 
 
DOI no: 10.1016/S0969-2126(97)00178-0 Structure 5:187-202 (1997)
PubMed id: 9032074  
 
 
The open conformation of a Pseudomonas lipase.
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, A.McPherson.
 
  ABSTRACT  
 
BACKGROUND:. The interfacial activation of lipases results primarily from conformational changes in the enzymes which expose the active site and provide a hydrophobic surface for interaction with the lipid substrate. Comparison of the crystallization conditions used and the structures observed for a variety of lipases suggests that the enzyme conformation is dependent on solution conditions. Pseudomonas cepacia lipase (PCL) was crystallized in conditions from which the open, active conformation of the enzyme was expected. Its three-dimensional structure was determined independently in three different laboratories and was compared with the previously reported closed conformations of the closely related lipases from Pseudomonas glumae (PGL) and Chromobacterium viscosum (CVL). These structures provide new insights into the function of this commercially important family of lipases. RESULTS:. The three independent structures of PCL superimpose with only small differences in the mainchain conformations. As expected, the observed conformation reveals a catalytic site exposed to the solvent. Superposition of PCL with the PGL and CVL structures indicates that the rearrangement from the closed to the open conformation involves three loops. The largest movement involves a 40 residue stretch, within which a helical segment moves to afford access to the catalytic site. A hydrophobic cleft that is presumed to be the lipid binding site is formed around the active site. CONCLUSIONS:. The interfacial activation of Pseudomonas lipases involves conformational rearrangements of surface loops and appears to conform to models of activation deduced from the structures of fungal and mammalian lipases. Factors controlling the conformational rearrangement are not understood, but a comparison of crystallization conditions and observed conformation suggests that the conformation of the protein is determined by the solution conditions, perhaps by the dielectric constant.
 
  Selected figure(s)  
 
Figure 7.
Figure 7. Comparison of the open and closed conformations. Helix a5 of PGL is superimposed onto the molecular surface of PCL. The active site is colored as in Figure 2c. (Figure produced using the program GRASP [45].)
 
  The above figure is reprinted by permission from Cell Press: Structure (1997, 5, 187-202) copyright 1997.  
  Figure was selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20857506 E.Papaleo, and G.Invernizzi (2011).
Conformational plasticity of the calcium-binding pocket in the Burkholderia glumae lipase: Remodeling induced by mutation of calcium coordinating residues.
  Biopolymers, 95, 117-126.  
20444688 M.Li, C.Chen, D.R.Davies, and T.K.Chiu (2010).
Induced-fit mechanism for prolyl endopeptidase.
  J Biol Chem, 285, 21487-21495.
PDB codes: 3iuj 3iul 3ium 3iun 3iuq 3iur 3ivm
19885896 E.García-Urdiales, E.Busto, N.Ríos-Lombardía, V.Gotor-Fernández, and V.Gotor (2009).
Computational study of the lipase-mediated desymmetrisation of 2-substituted-propane-1,3-diamines.
  Chembiochem, 10, 2875-2883.  
19476626 P.Trodler, R.D.Schmid, and J.Pleiss (2009).
Modeling of solvent-dependent conformational transitions in Burkholderia cepacia lipase.
  BMC Struct Biol, 9, 38.  
19500339 R.Villa, M.Lotti, and P.Gatti-Lafranconi (2009).
Components of the E. coli envelope are affected by and can react to protein over-production in the cytoplasm.
  Microb Cell Fact, 8, 32.  
19816890 V.Lafaquière, S.Barbe, S.Puech-Guenot, D.Guieysse, J.Cortés, P.Monsan, T.Siméon, I.André, and M.Remaud-Siméon (2009).
Control of lipase enantioselectivity by engineering the substrate binding site and access channel.
  Chembiochem, 10, 2760-2771.  
18753135 J.E.Burke, Y.H.Hsu, R.A.Deems, S.Li, V.L.Woods, and E.A.Dennis (2008).
A Phospholipid Substrate Molecule Residing in the Membrane Surface Mediates Opening of the Lid Region in Group IVA Cytosolic Phospholipase A2.
  J Biol Chem, 283, 31227-31236.  
  19609386 J.G.Mala, and S.Takeuchi (2008).
Understanding structural features of microbial lipases-an overview.
  Anal Chem Insights, 3, 9.  
18987131 K.Kuwahara, C.Angkawidjaja, H.Matsumura, Y.Koga, K.Takano, and S.Kanaya (2008).
Importance of the Ca2+-binding sites in the N-catalytic domain of a family I.3 lipase for activity and stability.
  Protein Eng Des Sel, 21, 737-744.
PDB codes: 2zj6 2zj7
18154980 P.Trodler, J.Nieveler, M.Rusnak, R.D.Schmid, and J.Pleiss (2008).
Rational design of a new one-step purification strategy for Candida antarctica lipase B by ion-exchange chromatography.
  J Chromatogr A, 1179, 161-167.  
17054124 G.Fernandez-Lorente, J.M.Palomo, Z.Cabrera, R.Fernandez-Lafuente, and J.M.Guisán (2007).
Improved catalytic properties of immobilized lipases by the presence of very low concentrations of detergents in the reaction medium.
  Biotechnol Bioeng, 97, 242-250.  
17586771 J.J.Petkowski, M.Chruszcz, M.D.Zimmerman, H.Zheng, T.Skarina, O.Onopriyenko, M.T.Cymborowski, K.D.Koclega, A.Savchenko, A.Edwards, and W.Minor (2007).
Crystal structures of TM0549 and NE1324--two orthologs of E. coli AHAS isozyme III small regulatory subunit.
  Protein Sci, 16, 1360-1367.
PDB codes: 2fgc 2pc6
17106678 S.Kakugawa, S.Fushinobu, T.Wakagi, and H.Shoun (2007).
Characterization of a thermostable carboxylesterase from the hyperthermophilic bacterium Thermotoga maritima.
  Appl Microbiol Biotechnol, 74, 585-591.  
16491501 I.Lavandera, S.Fernández, J.Magdalena, M.Ferrero, H.Grewal, C.K.Savile, R.J.Kazlauskas, and V.Gotor (2006).
Remote interactions explain the unusual regioselectivity of lipase from Pseudomonas cepacia toward the secondary hydroxyl of 2'-deoxynucleosides.
  Chembiochem, 7, 693-698.  
16283542 G.Lin, W.C.Liao, and Z.H.Ku (2005).
Quantitative structure-activity relationships for the pre-steady state of Pseudomonas species lipase inhibitions by p-nirophenyl-N-substituted carbamates.
  Protein J, 24, 201-207.  
16176589 S.Y.Chiou, C.Y.Lai, L.Y.Lin, and G.Lin (2005).
Probing stereoselective inhibition of the acyl binding site of cholesterol esterase with four diastereomers of 2'-N-alpha-methylbenzylcarbamyl-1, 1'-bi-2-naphthol.
  BMC Biochem, 6, 17.  
15554150 C.C.Akoh, G.C.Lee, and J.F.Shaw (2004).
Protein engineering and applications of Candida rugosa lipase isoforms.
  Lipids, 39, 513-526.  
15378387 E.A.Snellman, and R.R.Colwell (2004).
Acinetobacter lipases: molecular biology, biochemical properties and biotechnological potential.
  J Ind Microbiol Biotechnol, 31, 391-400.  
15213385 J.D.Cheeseman, A.Tocilj, S.Park, J.D.Schrag, and R.J.Kazlauskas (2004).
Structure of an aryl esterase from Pseudomonas fluorescens.
  Acta Crystallogr D Biol Crystallogr, 60, 1237-1243.
PDB code: 1va4
12619699 A.Tanaka, H.Sugimoto, Y.Muta, T.Mizuno, K.Senoo, H.Obata, and K.Inouye (2003).
Differential scanning calorimetry of the effects of Ca2+ on the thermal unfolding of Pseudomonas cepacia lipase.
  Biosci Biotechnol Biochem, 67, 207-210.  
12855696 G.Calero, P.Gupta, M.C.Nonato, S.Tandel, E.R.Biehl, S.L.Hofmann, and J.Clardy (2003).
The crystal structure of palmitoyl protein thioesterase-2 (PPT2) reveals the basis for divergent substrate specificities of the two lysosomal thioesterases, PPT1 and PPT2.
  J Biol Chem, 278, 37957-37964.
PDB code: 1pja
12611897 J.Morlon-Guyot, M.Helmy, S.Lombard-Frasca, D.Pignol, G.Piéroni, and B.Beaumelle (2003).
Identification of the ricin lipase site and implication in cytotoxicity.
  J Biol Chem, 278, 17006-17011.  
12732651 R.Sanishvili, A.F.Yakunin, R.A.Laskowski, T.Skarina, E.Evdokimova, A.Doherty-Kirby, G.A.Lajoie, J.M.Thornton, C.H.Arrowsmith, A.Savchenko, A.Joachimiak, and A.M.Edwards (2003).
Integrating structure, bioinformatics, and enzymology to discover function: BioH, a new carboxylesterase from Escherichia coli.
  J Biol Chem, 278, 26039-26045.
PDB code: 1m33
12084074 C.Alquati, L.De Gioia, G.Santarossa, L.Alberghina, P.Fantucci, and M.Lotti (2002).
The cold-active lipase of Pseudomonas fragi. Heterologous expression, biochemical characterization and molecular modeling.
  Eur J Biochem, 269, 3321-3328.  
11859083 S.T.Jeong, H.K.Kim, S.J.Kim, S.W.Chi, J.G.Pan, T.K.Oh, and S.E.Ryu (2002).
Novel zinc-binding center and a temperature switch in the Bacillus stearothermophilus L1 lipase.
  J Biol Chem, 277, 17041-17047.
PDB code: 1ku0
11418564 G.J.McCool, and M.C.Cannon (2001).
PhaC and PhaR are required for polyhydroxyalkanoic acid synthase activity in Bacillus megaterium.
  J Bacteriol, 183, 4235-4243.  
11453990 M.Luić, S.Tomić, I.Lescić, E.Ljubović, D.Sepac, V.Sunjić, L.Vitale, W.Saenger, and B.Kojic-Prodić (2001).
Complex of Burkholderia cepacia lipase with transition state analogue of 1-phenoxy-2-acetoxybutane: biocatalytic, structural and modelling study.
  Eur J Biochem, 268, 3964-3973.
PDB code: 1hqd
11092545 G.Lin, W.C.Liao, and S.Y.Chiou (2000).
Quantitative structure-activity relationships for the pre-steady-state inhibition of cholesterol esterase by 4-nitrophenyl-N-substituted carbamates.
  Bioorg Med Chem, 8, 2601-2607.  
10898867 J.S.Shin, S.Luque, and A.M.Klibanov (2000).
Improving lipase enantioselectivity in organic solvents by forming substrate salts with chiral agents.
  Biotechnol Bioeng, 69, 577-583.  
10980451 K.Liebeton, A.Zonta, K.Schimossek, M.Nardini, D.Lang, B.W.Dijkstra, M.T.Reetz, and K.E.Jaeger (2000).
Directed evolution of an enantioselective lipase.
  Chem Biol, 7, 709-718.  
11099797 R.Rosenstein, and F.Götz (2000).
Staphylococcal lipases: biochemical and molecular characterization.
  Biochimie, 82, 1005-1014.  
  10892799 T.Schulz, J.Pleiss, and R.D.Schmid (2000).
Stereoselectivity of Pseudomonas cepacia lipase toward secondary alcohols: a quantitative model.
  Protein Sci, 9, 1053-1062.  
10747780 Y.Jia, T.J.Kappock, T.Frick, A.J.Sinskey, and J.Stubbe (2000).
Lipases provide a new mechanistic model for polyhydroxybutyrate (PHB) synthases: characterization of the functional residues in Chromatium vinosum PHB synthase.
  Biochemistry, 39, 3927-3936.  
9890877 J.W.Simons, M.D.van Kampen, I.Ubarretxena-Belandia, R.C.Cox, C.M.Alves dos Santos, M.R.Egmond, and H.M.Verheij (1999).
Identification of a calcium binding site in Staphylococcus hyicus lipase: generation of calcium-independent variants.
  Biochemistry, 38, 2.  
10320365 J.W.Simons, R.C.Cox, M.R.Egmond, and H.M.Verheij (1999).
Rational design of alpha-keto triglyceride analogues as inhibitors for Staphylococcus hyicus lipase.
  Biochemistry, 38, 6346-6351.  
10547694 K.E.Jaeger, B.W.Dijkstra, and M.T.Reetz (1999).
Bacterial biocatalysts: molecular biology, three-dimensional structures, and biotechnological applications of lipases.
  Annu Rev Microbiol, 53, 315-351.  
10607665 M.Nardini, and B.W.Dijkstra (1999).
Alpha/beta hydrolase fold enzymes: the family keeps growing.
  Curr Opin Struct Biol, 9, 732-737.  
9590625 A.Ibrik, H.Chahinian, N.Rugani, L.Sarda, and L.C.Comeau (1998).
Biochemical and structural characterization of triacylglycerol lipase from Penicillium cyclopium.
  Lipids, 33, 377-384.  
9720251 J.Pleiss, M.Fischer, and R.D.Schmid (1998).
Anatomy of lipase binding sites: the scissile fatty acid binding site.
  Chem Phys Lipids, 93, 67-80.  
9667912 R.J.Kazlauskas, and H.K.Weber (1998).
Improving hydrolases for organic synthesis.
  Curr Opin Chem Biol, 2, 121-126.  
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.