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

References listed in PDB file

Key reference

Title

Structural basis of phospholipase a2 inhibition for the synthesis of prostaglandins by the plant alkaloid aristolochic acid from a 1.7 a crystal structure.

Authors

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

Ref.

Biochemistry, 2002, 41, 10914-10919. [DOI no: 10.1021/bi0258593]

PubMed id

12206661

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).

Secondary reference #1

Title

First structural evidence of antiinflammatory action of vitamin e (2,5,7,8-Tetramethyl-2-(4',8',12'- Trimethyltridecyl)-6-Chromanol) through its binding to phospholipase a2 specifically: crystal structure of a complex formed between phospholipase a2 and vitamin e at 1.80 resolution

Authors

V.Chandra, J.Jasti, P.Kaur, M.Perbandt, Ch.Betzel, T.P.Singh.

Ref.

TO BE PUBLISHED ...

Secondary reference #2

Title

Three-Dimensional structure of a presynaptic neurotoxic phospholipase a2 from daboia russelli pulchella at 2.4 a resolution.

Authors

V.Chandra, P.Kaur, A.Srinivasan, T.P.Singh.

Ref.

J Mol Biol, 2000, 296, 1117-1126. [DOI no: 10.1006/jmbi.2000.3537]

PubMed id

10686108

Figure 3.
Figure 3. (a) Superimposition of C^α traces of DPLA[2] (thick lines) and VPLA[2] (thin lines). The r.m.s. difference for the C^α atoms is 1.2 Å. The corresponding shifts for the neurotoxic (55–61 and 85–94), and anticoagulant (53–77) fragments are 1.8 Å and 1.3 Å, respectively. (b) Protruding side-chains of basic residues for the anticoagulant site.

Figure 4.
Figure 4. (a) The association of molecules A and B showing a number of residues from both the molecules (black) and solvent molecules (red) involved in the interactions between two molecules: molecule A, Leu2, Leu17, Ala18, Ile19, Pro20, Trp31, Arg43, Phe46, Ser70, Arg72, Met118, Leu119 and Asp122; molecule B, Thr36, Ala40, Arg43, Phe46, Val47, Asn54, Glu97, Lys100, Ile104, Gln108, Asn111, Leu130, Lys131 and Cys133 and 31 solvent molecules. (b) Spatially two adjacent fragments 55–61 and 85–94. The segment 55–61 forms a β-turn I with a hydrogen bond between Leu55 (O) and Cys61 (N). A tight loop, 85-94, is stabilized by a number of intra-loop hydrogen bonds which are indicated by dotted lines. The inter-segmental hydrogen bonds (red, broken lines) are also indicated.

The above figures are reproduced from the cited reference with permission from Elsevier