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Hydrolase PDB id
1ein
Jmol
Contents
Protein chains
269 a.a. *
Ligands
PLC ×3
Waters ×184
* Residue conservation analysis
PDB id:
1ein
Name: Hydrolase
Title: The structural origins of interfacial activation in thermomyces (humicola) lanuginosa lipase
Structure: Lipase. Chain: a, b, c. Ec: 3.1.1.3
Source: Thermomyces lanuginosus. Organism_taxid: 5541
Resolution:
3.00Å     R-factor:   0.210     R-free:   0.241
Authors: A.M.Brozozowski,H.Savage
Key ref:
A.M.Brzozowski et al. (2000). Structural origins of the interfacial activation in Thermomyces (Humicola) lanuginosa lipase. Biochemistry, 39, 15071-15082. PubMed id: 11106485 DOI: 10.1021/bi0013905
Date:
26-Feb-00     Release date:   20-Dec-00    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
O59952  (LIP_THELA) -  Lipase
Seq:
Struc: 		291 a.a.
269 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!
  Biological process     lipid metabolic process   2 terms 
  Biochemical function     hydrolase activity     3 terms  

 

 
    reference    
 
 
DOI no: 10.1021/bi0013905 Biochemistry 39:15071-15082 (2000)
PubMed id: 11106485  
 
 
Structural origins of the interfacial activation in Thermomyces (Humicola) lanuginosa lipase.
A.M.Brzozowski, H.Savage, C.S.Verma, J.P.Turkenburg, D.M.Lawson, A.Svendsen, S.Patkar.
 
  ABSTRACT  
 
The already known X-ray structures of lipases provide little evidence about initial, discrete structural steps occurring in the first phases of their activation in the presence of lipids (process referred to as interfacial activation). To address this problem, five new Thermomyces (formerly Humicola) lanuginosa lipase (TlL) crystal structures have been solved and compared with four previously reported structures of this enzyme. The bias coming from different crystallization media has been minimized by the growth of all crystals under the same crystallization conditions, in the presence of detergent/lipid analogues, with low or high ionic strength as the only main variable. Resulting structures and their characteristic features allowed the identification of three structurally distinct species of this enzyme: low activity form (LA), activated form (A), and fully Active (FA) form. The isomerization of the Cys268-Cys22 disulfide, synchronized with the formation of a new, short alpha(0) helix and flipping of the Arg84 (Arginine switch) located in the lid's proximal hinge, have been postulated as the key, structural factors of the initial transitions between LA and A forms. The experimental results were supplemented by theoretical calculations. The magnitude of the activation barrier between LA (ground state) and A (end state) forms of TlL (10.6 kcal/mol) is comparable to the enthalpic barriers typical for ring flips and disulfide isomerizations at ambient temperatures. This suggests that the sequence of the structural changes, as exemplified in various TlL crystal structures, mirror those that may occur during interfacial activation.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21351321 S.Longhi, V.Belle, A.Fournel, B.Guigliarelli, and F.Carrière (2011).
Probing structural transitions in both structured and disordered proteins using site-directed spin-labeling EPR spectroscopy.
  J Pept Sci, 17, 315-328.  
20150178 D.Y.Colin, P.Deprez-Beauclair, N.Silva, L.Infantes, and B.Kerfelec (2010).
Modification of pancreatic lipase properties by directed molecular evolution.
  Protein Eng Des Sel, 23, 365-373.  
20812327 S.Rehm, P.Trodler, and J.Pleiss (2010).
Solvent-induced lid opening in lipases: a molecular dynamics study.
  Protein Sci, 19, 2122-2130.  
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.  
19527641 S.Santini, J.M.Crowet, A.Thomas, M.Paquot, M.Vandenbol, P.Thonart, J.P.Wathelet, C.Blecker, G.Lognay, R.Brasseur, L.Lins, and B.Charloteaux (2009).
Study of Thermomyces lanuginosa lipase in the presence of tributyrylglycerol and water.
  Biophys J, 96, 4814-4825.  
18658138 S.Chen, X.Tong, R.W.Woodard, G.Du, J.Wu, and J.Chen (2008).
Identification and characterization of bacterial cutinase.
  J Biol Chem, 283, 25854-25862.  
  18765911 Y.Sun, M.Li, Y.Zhang, L.Liu, Y.Liu, Z.Liu, X.Li, and Z.Lou (2008).
Crystallization and preliminary crystallographic analysis of Gibberella zeae extracellular lipase.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 64, 813-815.  
17306756 J.Lee, and S.Safe (2007).
Coactivation of estrogen receptor alpha (ER alpha)/Sp1 by vitamin D receptor interacting protein 150 (DRIP150).
  Arch Biochem Biophys, 461, 200-210.  
17728256 R.Meier, T.Drepper, V.Svensson, K.E.Jaeger, and U.Baumann (2007).
A calcium-gated lid and a large beta-roll sandwich are revealed by the crystal structure of extracellular lipase from Serratia marcescens.
  J Biol Chem, 282, 31477-31483.
PDB codes: 2qua 2qub
16088345 H.S.Ryu, H.K.Kim, W.C.Choi, M.H.Kim, S.Y.Park, N.S.Han, T.K.Oh, and J.K.Lee (2006).
New cold-adapted lipase from Photobacterium lipolyticum sp. nov. that is closely related to filamentous fungal lipases.
  Appl Microbiol Biotechnol, 70, 321-326.  
16767259 N.S.Hatzakis, H.Engelkamp, K.Velonia, J.Hofkens, P.C.Christianen, A.Svendsen, S.A.Patkar, J.Vind, J.C.Maan, A.E.Rowan, and R.J.Nolte (2006).
Synthesis and single enzyme activity of a clicked lipase-BSA hetero-dimer.
  Chem Commun (Camb), 0, 2012-2014.  
15625066 J.E.Lee, K.Kim, J.C.Sacchettini, C.V.Smith, and S.Safe (2005).
DRIP150 coactivation of estrogen receptor alpha in ZR-75 breast cancer cells is independent of LXXLL motifs.
  J Biol Chem, 280, 8819-8830.  
15688435 M.Zheng, K.Ginalski, L.Rychlewski, and N.V.Grishin (2005).
Protein domain of unknown function DUF1023 is an alpha/beta hydrolase.
  Proteins, 59, 1-6.  
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.  
15557256 G.Fuentes, A.Ballesteros, and C.S.Verma (2004).
Specificity in lipases: a computational study of transesterification of sucrose.
  Protein Sci, 13, 3092-3103.  
15103133 K.E.McAuley, A.Svendsen, S.A.Patkar, and K.S.Wilson (2004).
Structure of a feruloyl esterase from Aspergillus niger.
  Acta Crystallogr D Biol Crystallogr, 60, 878-887.
PDB codes: 1uwc 1uza
12931010 D.Marsh (2003).
Lipid-binding proteins: structure of the phospholipid ligands.
  Protein Sci, 12, 2109-2117.  
12080103 M.Ã.˜.Jensen, T.R.Jensen, K.Kjaer, T.Bjørnholm, O.G.Mouritsen, and G.H.Peters (2002).
Orientation and conformation of a lipase at an interface studied by molecular dynamics simulations.
  Biophys J, 83, 98.  
11895431 S.Yapoudjian, M.G.Ivanova, A.M.Brzozowski, S.A.Patkar, J.Vind, A.Svendsen, and R.Verger (2002).
Binding of Thermomyces (Humicola) lanuginosa lipase to the mixed micelles of cis-parinaric acid/NaTDC.
  Eur J Biochem, 269, 1613-1621.
PDB code: 1gt6
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.