PDBsum entry 1fv0

Toxin

PDB id: 1fv0

Contents

Protein chains

121 a.a. *

Ligands

SO4 ×4

ACT

9AR

GOL ×2

DIO ×2

Waters ×315

* Residue conservation analysis

PDB id:

1fv0

Name:

Toxin

Title:

First structural evidence of the inhibition of phospholipase a2 by aristolochic acid: crystal structure of a complex formed between phospholipase a2 and aristolochic acid

Structure:

Phospholipase a2. Chain: a, b

Source:

Daboia russellii pulchella. Organism_taxid: 97228. Strain: pulchella. Secretion: venom

Resolution:

1.70Å R-factor: 0.184 R-free: 0.201

Authors:

V.Chandra,J.Jasti,P.Kaur,A.Srinivasan,C.Betzel,T.P.Singh

Key ref:

V.Chandra et al. (2002). Structural basis of phospholipase A2 inhibition for the synthesis of prostaglandins by the plant alkaloid aristolochic acid from a 1.7 A crystal structure. Biochemistry, 41, 10914-10919. PubMed id: 12206661 DOI: 10.1021/bi0258593

Date:

18-Sep-00 Release date: 28-Aug-02

Protein chains

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⁺

1,2-diacyl-sn-glycero-3-phosphocholine + H2O = 1-acyl-sn-glycero-3- phosphocholine + fatty acid (Bound ligand (Het Group name = ACT) matches with 60.00% similarity) + H(+)

• Cofactor: Ca(2+)

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

reference

DOI no: 10.1021/bi0258593

Biochemistry 41:10914-10919 (2002)

PubMed id: 12206661

Structural basis of phospholipase A2 inhibition for the synthesis of prostaglandins by the plant alkaloid aristolochic acid from a 1.7 A crystal structure.

V.Chandra, J.Jasti, P.Kaur, A.Srinivasan, C.h.Betzel, T.P.Singh.

ABSTRACT

This is the first structural observation of a plant product showing high affinity for phospholipase A(2) and regulating the synthesis of arachidonic acid, an intermediate in the production of prostaglandins. The crystal structure of a complex formed between Vipera russelli phospholipase A(2) and a plant alkaloid aristolochic acid has been determined and refined to 1.7 A resolution. The structure contains two crystallographically independent molecules of phospholipase A(2) in the form of an asymmetric dimer with one molecule of aristolochic acid bound to one of them specifically. The most significant differences introduced by asymmetric molecular association in the structures of two molecules pertain to the conformations of their calcium binding loops, beta-wings, and the C-terminal regions. These differences are associated with a unique conformational behavior of Trp(31). Trp(31) is located at the entrance of the characteristic hydrophobic channel which works as a passage to the active site residues in the enzyme. In the case of molecule A, Trp(31) is found at the interface of two molecules and it forms a number of hydrophobic interactions with the residues of molecule B. Consequently, it is pulled outwardly, leaving the mouth of the hydrophobic channel wide open. On the other hand, Trp(31) in molecule B is exposed to the surface and moves inwardly due to the polar environment on the molecular surface, thus narrowing the opening of the hydrophobic channel. As a result, the aristolochic acid is bound to molecule A only while the binding site of molecule B is empty. It is noteworthy that the most critical interactions in the binding of aristolochic acid are provided by its OH group which forms two hydrogen bonds, one each with His(48) and Asp(49).