PDBsum entry 2b17

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Hydrolase PDB id
Protein chain
121 a.a. *
SO4 ×2
Waters ×85
* Residue conservation analysis
PDB id:
Name: Hydrolase
Title: Specific binding of non-steroidal anti-inflammatory drugs (nsaids) to phospholipase a2: crystal structure of the complex formed between phospholipase a2 and diclofenac at 2.7 a resolution:
Structure: Phospholipase a2 vrv-pl-viiia. Chain: a. Synonym: phosphatidylcholine 2-acylhydrolase, dpla2. Ec:
Source: Daboia russellii pulchella. Organism_taxid: 97228. Strain: pulchella
2.71Å     R-factor:   0.192     R-free:   0.211
Authors: N.Singh,T.Jabeen,S.Sharma,T.P.Singh
Key ref:
N.Singh et al. (2006). Specific binding of non-steroidal anti-inflammatory drugs (NSAIDs) to phospholipase A(2): structure of the complex formed between phospholipase A(2) and diclofenac at 2.7 A resolution. Acta Crystallogr D Biol Crystallogr, 62, 410-416. PubMed id: 16552142 DOI: 10.1107/S0907444906003660
15-Sep-05     Release date:   04-Oct-05    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P59071  (PA28_DABRR) -  Basic phospholipase A2 VRV-PL-VIIIa
121 a.a.
121 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - Phospholipase A(2).
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Phosphatidylcholine + H2O = 1-acylglycerophosphocholine + a carboxylate
+ H(2)O
= 1-acylglycerophosphocholine
Bound ligand (Het Group name = DIF)
matches with 40.00% similarity
      Cofactor: Ca(2+)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   2 terms 
  Biological process     lipid metabolic process   3 terms 
  Biochemical function     hydrolase activity     4 terms  


DOI no: 10.1107/S0907444906003660 Acta Crystallogr D Biol Crystallogr 62:410-416 (2006)
PubMed id: 16552142  
Specific binding of non-steroidal anti-inflammatory drugs (NSAIDs) to phospholipase A(2): structure of the complex formed between phospholipase A(2) and diclofenac at 2.7 A resolution.
N.Singh, T.Jabeen, S.Sharma, R.K.Somvanshi, S.Dey, A.Srinivasan, T.P.Singh.
Type IIA secretory phospholipase A(2) (PLA(2)) enzymes catalyze the hydrolysis of the sn-2 ester bond of glycerophospholipids to release fatty acids and lysophospholipids. In order to elucidate the role of PLA(2) in inflammatory disorders and to determine the mode of binding of non-steroidal anti-inflammatory drugs (NSAIDs) to PLA(2), the detailed three-dimensional structure of a complex formed between a group IIA PLA(2) from Daboia russelli pulchella and 2-[(2,6-dichlorophenyl)amino]benzeneacetic acid (diclofenac) has been determined. The preformed complex was crystallized by equilibrating the protein solution against a mixture of 0.20 M ammonium sulfate and 30% PEG 4000. The crystals belong to space group P4(3), with unit-cell parameters a = b = 53.0, c = 48.4 A. The structure was solved by the molecular-replacement method and refined to R(cryst) and R(free) factors of 0.192 and 0.211, respectively, using reflections to 2.7 A resolution. The structure showed that diclofenac occupies a very favourable position in the centre of the substrate-binding hydrophobic channel that allows a number of intermolecular interactions. The binding mode of diclofenac involved crucial interactions with important residues for substrate recognition such as Asp49, His48 and Gly30. In addition, it included three new interactions involving its Cl atoms with Phe5, Ala18 and Tyr22. It also showed an extensive network of hydrophobic interactions involving almost all of the residues of the substrate-binding hydrophobic channel. The binding affinity of diclofenac was determined using surface plasmon resonance, which gave an equilibrium constant of 4.8 +/- 0.2 x 10(-8) M.
  Selected figure(s)  
Figure 4.
Figure 4 A stereoview of showing the interactions of diclofenac with PLA[2]. Hydrogen bonds are shown in red, while van der Waals interactions with Cl atoms are indicated in black. The figure was drawn with PyMOL (DeLano, 2002[DeLano, W. L. (2002). The PyMol Molecular Graphics System. DeLano Scientific, San Carlos, CA, USA. .]).
Figure 5.
Figure 5 The superimposition of diclofenac from the present complex with PLA[2] (yellow) on diclofenac from the complex with COX-2 (blue) and on uncomplexed diclofenac (green).
  The above figures are reprinted by permission from the IUCr: Acta Crystallogr D Biol Crystallogr (2006, 62, 410-416) copyright 2006.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20823552 F.Pavelcík, and J.Václavík (2010).
Performance of phased rotation, conformation and translation function: accurate protein model building with tripeptidic and tetrapeptidic fragments.
  Acta Crystallogr D Biol Crystallogr, 66, 1012-1023.  
20470236 T.J.Gan (2010).
Diclofenac: an update on its mechanism of action and safety profile.
  Curr Med Res Opin, 26, 1715-1731.  
18074396 R.L.Rich, and D.G.Myszka (2007).
Survey of the year 2006 commercial optical biosensor literature.
  J Mol Recognit, 20, 300-366.  
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