PDBsum entry 2arm

Hydrolase

PDB id: 2arm

Contents

Protein chain

121 a.a. *

Ligands

OIN

SO4 ×4

Waters ×247

* Residue conservation analysis

PDB id:

2arm

Name:

Hydrolase

Title:

Crystal structure of the complex of phospholipase a2 with a natural compound atropine at 1.2 a resolution

Structure:

Phospholipase a2 vrv-pl-viiia. Chain: a. Synonym: phosphatidylcholine 2-acylhydrolase, dpla2. Ec: 3.1.1.4

Source:

Daboia russellii pulchella. Organism_taxid: 97228

Resolution:

1.23Å R-factor: 0.189 R-free: 0.204

Authors:

N.Singh,A.Pal,T.Jabeen,S.Sharma,M.Perbandt,C.Betzel,T.P.Singh

Key ref:

N.Singh et al. (2006). Crystal structures of the complexes of a group IIA phospholipase A2 with two natural anti-inflammatory agents, anisic acid, and atropine reveal a similar mode of binding. Proteins, 64, 89-100. PubMed id: 16596639 DOI: 10.1002/prot.20970

Date:

20-Aug-05 Release date: 20-Sep-05

Protein chain

P59071  (PA2B8_DABRR) -  Basic phospholipase A2 VRV-PL-VIIIa from Daboia russelii

Seq: 121 a.a.

Struc: 121 a.a.

Enzyme reactions

• Enzyme class: E.C.3.1.1.4 - phospholipase A2.
• Reaction: a 1,2-diacyl-sn-glycero-3-phosphocholine + H2O = a 1-acyl-sn-glycero-3- phosphocholine + a fatty acid + H⁺
• Cofactor: Ca(2+)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1002/prot.20970

Proteins 64:89-100 (2006)

PubMed id: 16596639

Crystal structures of the complexes of a group IIA phospholipase A2 with two natural anti-inflammatory agents, anisic acid, and atropine reveal a similar mode of binding.

N.Singh, T.Jabeen, A.Pal, S.Sharma, M.Perbandt, C.Betzel, T.P.Singh.

ABSTRACT

Secretory low molecular weight phospholipase A(2)s (PLA(2)s) are believed to be involved in the release of arachidonic acid, a precursor for the biosynthesis of pro-inflammatory eicosanoids. Therefore, the specific inhibitors of these enzymes may act as potent anti-inflammatory agents. Similarly, the compounds with known anti-inflammatory properties should act as specific inhibitors. Two plant compounds, (a) anisic acid (4-methoxy benzoic acid) and (b) atropine (8-methyl-8-azabicyclo oct-3-hydroxy-2-phenylpropanoate), have been used in various inflammatory disorders. Both compounds (a) and (b) have been found to inhibit PLA(2) activity having binding constants of 4.5 x 10(-5) M and 2.1 x 10(-8) M, respectively. A group IIA PLA(2) was isolated and purified from the venom of Daboia russelli pulchella (DRP) and its complexes were made with anisic acid and atropine. The crystal structures of the two complexes (i) and (ii) of PLA(2) with compounds (a) and (b) have been determined at 1.3 and 1.2 A resolutions, respectively. The high-quality observed electron densities for the two compounds allowed the accurate determinations of their atomic positions. The structures revealed that these compounds bound to the enzyme at the substrate - binding cleft and their positions were stabilized by networks of hydrogen bonds and hydrophobic interactions. The most characteristic interactions involving Asp 49 and His 48 were clearly observed in both complexes, although the residues that formed hydrophobic interactions with these compounds were not identical because their positions did not exactly superimpose in the large substrate-binding hydrophobic channel. Owing to a relatively small size, the structure of anisic acid did not alter upon binding to PLA(2), while that of atropine changed significantly when compared with its native crystal structure. The conformation of the protein also did not show notable changes upon the bindings of these ligands. The mode of binding of anisic acid to the present group II PLA(2) is almost identical to its binding with bovine pancreatic PLA(2) of group I. On the other hand, the binding of atropine to PLA(2) is similar to that of another plant alkaloid aristolochic acid.

Selected figure(s)

Figure 5.
Figure 5.

Figure 6.
Figure 6. The superimposition of atropine (yellow) from the present structure on its structure in the uncomplexed states (blue).

The above figures are reprinted by permission from John Wiley & Sons, Inc.: Proteins (2006, 64, 89-100) copyright 2006.

Figures were selected by an automated process.