PDBsum entry 1thg

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Hydrolase(carboxylic esterase) PDB id
Protein chain
544 a.a. *
Waters ×343
* Residue conservation analysis
PDB id:
Name: Hydrolase(carboxylic esterase)
Title: 1.8 angstroms refined structure of the lipase from geotrichu
Structure: Lipase. Chain: a. Engineered: yes
Source: Galactomyces geotrichum. Ascomycetes. Organism_taxid: 27317. Strain: atcc 34614
1.80Å     R-factor:   0.157    
Authors: J.D.Schrag,M.Cygler
Key ref: J.D.Schrag and M.Cygler (1993). 1.8 A refined structure of the lipase from Geotrichum candidum. J Mol Biol, 230, 575-591. PubMed id: 8464065
28-Jul-92     Release date:   31-Oct-93    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P79066  (LIP1_GEOFE) -  Lipase 1
563 a.a.
544 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: E.C.  - Triacylglycerol lipase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Triacylglycerol + H2O = diacylglycerol + a carboxylate
+ 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   2 terms 
  Biochemical function     hydrolase activity     2 terms  


J Mol Biol 230:575-591 (1993)
PubMed id: 8464065  
1.8 A refined structure of the lipase from Geotrichum candidum.
J.D.Schrag, M.Cygler.
A lipase from the fungus Geotrichum candidum is one of only three interfacially activated lipases whose structures have been reported to date. We have previously reported the partially refined 2.2 A structure of this enzyme. We have subsequently extended the resolution and here report the fully refined 1.8 A structure of this lipase. The structure observed in the crystal is apparently not the lipolytic conformation, as the active site is not accessible from the surface of the molecule. A single large cavity is found in the interior of the molecule and extends from the catalytic Ser to two surface helices, suggesting that this face may be the region that interacts with the lipid interface. The mobility of local segments on this face is indicated by temperature factors larger than elsewhere in the molecule and by the observation of several residues whose side-chains are discretely disordered. These observations strongly suggest that this portion of the molecule is involved in interfacial and substrate binding, but the exact nature of the conformational changes induced by binding to the lipid interface can not be determined.

Literature references that cite this PDB file's key reference

  PubMed id Reference
19193735 S.G.Williams, and S.C.Lovell (2009).
The effect of sequence evolution on protein structural divergence.
  Mol Biol Evol, 26, 1055-1065.  
18800594 M.L.Verma, W.Azmi, and S.S.Kanwar (2008).
Microbial lipases: at the interface of aqueous and non-aqueous media. A review.
  Acta Microbiol Immunol Hung, 55, 265-294.  
17681228 A.L.Devonshire, R.Heidari, H.Z.Huang, B.D.Hammock, R.J.Russell, and J.G.Oakeshott (2007).
Hydrolysis of individual isomers of fluorogenic pyrethroid analogs by mutant carboxylesterases from Lucilia cuprina.
  Insect Biochem Mol Biol, 37, 891-902.  
16162494 H.J.Korza, and M.Bochtler (2005).
Pseudomonas aeruginosa LD-carboxypeptidase, a serine peptidase with a Ser-His-Glu triad and a nucleophilic elbow.
  J Biol Chem, 280, 40802-40812.
PDB codes: 1zrs 2aum 2aun
16110344 S.L.Cherukuvada, A.S.Seshasayee, K.Raghunathan, S.Anishetty, and G.Pennathur (2005).
Evidence of a double-lid movement in Pseudomonas aeruginosa lipase: insights from molecular dynamics simulations.
  PLoS Comput Biol, 1, e28.  
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.  
12216836 H.Chahinian, L.Nini, E.Boitard, J.P.Dubès, L.C.Comeau, and L.Sarda (2002).
Distinction between esterases and lipases: a kinetic study with vinyl esters and TAG.
  Lipids, 37, 653-662.  
11967565 S.Bencharit, C.L.Morton, E.L.Howard-Williams, M.K.Danks, P.M.Potter, and M.R.Redinbo (2002).
Structural insights into CPT-11 activation by mammalian carboxylesterases.
  Nat Struct Biol, 9, 337-342.
PDB code: 1k4y
11258933 H.González-Navarro, M.C.Bañó, and C.Abad (2001).
The closed/open model for lipase activation. Addressing intermediate active forms of fungal enzymes by trapping of conformers in water-restricted environments.
  Biochemistry, 40, 3174-3183.  
11517229 J.Shi, A.E.Boyd, Z.Radic, and P.Taylor (2001).
Reversibly bound and covalently attached ligands induce conformational changes in the omega loop, Cys69-Cys96, of mouse acetylcholinesterase.
  J Biol Chem, 276, 42196-42204.  
11084600 N.A.Turner, E.C.Needs, J.A.Khan, and E.N.Vulfson (2001).
Analysis of conformational states of Candida rugosa lipase in solution: implications for mechanism of interfacial activation and separation of open and closed forms.
  Biotechnol Bioeng, 72, 108-118.  
10022354 B.A.Thomas, W.B.Church, T.R.Lane, and B.D.Hammock (1999).
Homology model of juvenile hormone esterase from the crop pest, Heliothis virescens.
  Proteins, 34, 184-196.  
  10548044 J.Zuegg, K.Gruber, M.Gugganig, U.G.Wagner, and C.Kratky (1999).
Three-dimensional structures of enzyme-substrate complexes of the hydroxynitrile lyase from Hevea brasiliensis.
  Protein Sci, 8, 1990-2000.
PDB codes: 2yas 3yas 4yas 5yas 6yas 7yas
10404588 P.Heikinheimo, A.Goldman, C.Jeffries, and D.L.Ollis (1999).
Of barn owls and bankers: a lush variety of alpha/beta hydrolases.
  Structure, 7, R141-R146.  
9915834 Y.Bourne, P.Taylor, P.E.Bougis, and P.Marchot (1999).
Crystal structure of mouse acetylcholinesterase. A peripheral site-occluding loop in a tetrameric assembly.
  J Biol Chem, 274, 2963-2970.
PDB code: 1maa
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.  
9512023 F.Haeffner, T.Norin, and K.Hult (1998).
Molecular modeling of the enantioselectivity in lipase-catalyzed transesterification reactions.
  Biophys J, 74, 1251-1262.  
9720250 M.Holmquist (1998).
Insights into the molecular basis for fatty acyl specificities of lipases from Geotrichum candidum and Candida rugosa.
  Chem Phys Lipids, 93, 57-66.  
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
  9041628 S.Longhi, M.Mannesse, H.M.Verheij, G.H.De Haas, M.Egmond, E.Knoops-Mouthuy, and C.Cambillau (1997).
Crystal structure of cutinase covalently inhibited by a triglyceride analogue.
  Protein Sci, 6, 275-286.
PDB code: 1oxm
  9007978 S.R.Feaster, D.M.Quinn, and B.L.Barnett (1997).
Molecular modeling of the structures of human and rat pancreatic cholesterol esterases.
  Protein Sci, 6, 73-79.  
9228786 T.Arai, S.Yusa, K.Kirimura, and S.Usami (1997).
Cloning and sequencing of the cDNA encoding lipase I from Trichosporon fermentans WU-C12.
  FEMS Microbiol Lett, 152, 183-188.  
9331420 X.Wang, C.S.Wang, J.Tang, F.Dyda, and X.C.Zhang (1997).
The crystal structure of bovine bile salt activated lipase: insights into the bile salt activation mechanism.
  Structure, 5, 1209-1218.
PDB codes: 1akn 1aql
8703040 C.C.Yue, J.Muller-Greven, P.Dailey, G.Lozanski, V.Anderson, and S.Macintyre (1996).
Identification of a C-reactive protein binding site in two hepatic carboxylesterases capable of retaining C-reactive protein within the endoplasmic reticulum.
  J Biol Chem, 271, 22245-22250.  
  8703090 C.Robin, R.J.Russell, K.M.Medveczky, and J.G.Oakeshott (1996).
Duplication and divergence of the genes of the alpha-esterase cluster of Drosophila melanogaster.
  J Mol Evol, 43, 241-252.  
8913568 G.H.Peters, D.M.van Aalten, O.Edholm, S.Toxvaerd, and R.Bywater (1996).
Dynamics of proteins in different solvent systems: analysis of essential motion in lipases.
  Biophys J, 71, 2245-2255.  
8940153 J.A.Contreras, M.Karlsson, T.Osterlund, H.Laurell, A.Svensson, and C.Holm (1996).
Hormone-sensitive lipase is structurally related to acetylcholinesterase, bile salt-stimulated lipase, and several fungal lipases. Building of a three-dimensional model for the catalytic domain of hormone-sensitive lipase.
  J Biol Chem, 271, 31426-31430.  
9630920 J.C.Moore, and F.H.Arnold (1996).
Directed evolution of a para-nitrobenzyl esterase for aqueous-organic solvents.
  Nat Biotechnol, 14, 458-467.  
8743049 K.Gulomova, E.Ziomek, J.D.Schrag, K.Davranov, and M.Cygler (1996).
Purification and characterization of a Penicillium sp. lipase which discriminates against diglycerides.
  Lipids, 31, 379-384.  
  8606184 M.J.Brumlik, and J.T.Buckley (1996).
Identification of the catalytic triad of the lipase/acyltransferase from Aeromonas hydrophila.
  J Bacteriol, 178, 2060-2064.  
8672479 R.G.Brok, I.U.Belandia, N.Dekker, J.Tommassen, and H.M.Verheij (1996).
Escherichia coli outer membrane phospholipase A: role of two serines in enzymatic activity.
  Biochemistry, 35, 7787-7793.  
8805565 U.G.Wagner, M.Hasslacher, H.Griengl, H.Schwab, and C.Kratky (1996).
Mechanism of cyanogenesis: the crystal structure of hydroxynitrile lyase from Hevea brasiliensis.
  Structure, 4, 811-822.
PDB code: 1yas
7737973 F.Pries, J.Kingma, G.H.Krooshof, C.M.Jeronimus-Stratingh, A.P.Bruins, and D.B.Janssen (1995).
Histidine 289 is essential for hydrolysis of the alkyl-enzyme intermediate of haloalkane dehalogenase.
  J Biol Chem, 270, 10405-10411.  
7724558 I.Mingarro, C.Abad, and L.Braco (1995).
Interfacial activation-based molecular bioimprinting of lipolytic enzymes.
  Proc Natl Acad Sci U S A, 92, 3308-3312.  
7607235 K.M.Loomes (1995).
Structural organisation of human bile-salt-activated lipase probed by limited proteolysis and expression of a recombinant truncated variant.
  Eur J Biochem, 230, 607-613.  
7592717 L.W.Tjoelker, C.Eberhardt, J.Unger, H.L.Trong, G.A.Zimmerman, T.M.McIntyre, D.M.Stafforini, S.M.Prescott, and P.W.Gray (1995).
Plasma platelet-activating factor acetylhydrolase is a secreted phospholipase A2 with a catalytic triad.
  J Biol Chem, 270, 25481-25487.  
7737187 M.C.Bertolini, J.D.Schrag, M.Cygler, E.Ziomek, D.Y.Thomas, and T.Vernet (1995).
Expression and characterization of Geotrichum candidum lipase I gene. Comparison of specificity profile with lipase II.
  Eur J Biochem, 228, 863-869.  
  7606666 M.Cygler, P.Grochulski, and J.D.Schrag (1995).
Structural determinants defining common stereoselectivity of lipases toward secondary alcohols.
  Can J Microbiol, 41, 289-296.  
8202471 L.Swenson, R.Green, R.Joerger, M.Haas, K.Scott, Y.Wei, U.Derewenda, D.M.Lawson, and Z.S.Derewenda (1994).
Crystallization and preliminary crystallographic studies of the precursor and mature forms of a neutral lipase from the fungus Rhizopus delemar.
  Proteins, 18, 301-306.  
8306978 M.C.Bertolini, L.Laramée, D.Y.Thomas, M.Cygler, J.D.Schrag, and T.Vernet (1994).
Polymorphism in the lipase genes of Geotrichum candidum strains.
  Eur J Biochem, 219, 119-125.  
7815893 M.Holmquist, M.Martinelle, I.G.Clausen, S.Patkar, A.Svendsen, and K.Hult (1994).
Trp89 in the lid of Humicola lanuginosa lipase is important for efficient hydrolysis of tributyrin.
  Lipids, 29, 599-603.  
  7833809 M.Norin, F.Haeffner, A.Achour, T.Norin, and K.Hult (1994).
Computer modeling of substrate binding to lipases from Rhizomucor miehei, Humicola lanuginosa, and Candida rugosa.
  Protein Sci, 3, 1493-1503.  
  8142901 P.Grochulski, Y.Li, J.D.Schrag, and M.Cygler (1994).
Two conformational states of Candida rugosa lipase.
  Protein Sci, 3, 82-91.
PDB code: 1trh
7656005 U.Derewenda, L.Swenson, R.Green, Y.Wei, G.G.Dodson, S.Yamaguchi, M.J.Haas, and Z.S.Derewenda (1994).
An unusual buried polar cluster in a family of fungal lipases.
  Nat Struct Biol, 1, 36-47.
PDB code: 1tia
  7914789 U.H.Mortensen, and K.Breddam (1994).
A conserved glutamic acid bridge in serine carboxypeptidases, belonging to the alpha/beta hydrolase fold, acts as a pH-dependent protein-stabilizing element.
  Protein Sci, 3, 838-842.  
8119594 J.G.Oakeshott, E.A.van Papenrecht, T.M.Boyce, M.J.Healy, and R.J.Russell (1993).
Evolutionary genetics of Drosophila esterases.
  Genetica, 90, 239-268.  
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.