PDBsum entry 1vpi

Neurotoxin

PDB id: 1vpi

Contents

Protein chain

122 a.a. *

Waters ×116

* Residue conservation analysis

PDB id:

1vpi

Name:

Neurotoxin

Title:

Phospholipase a2 inhibitor from vipoxin

Structure:

Phospholipase a2 inhibitor. Chain: a

Source:

Vipera ammodytes. Sand viper. Organism_taxid: 8704. Organ: venom gland

Biol. unit:

Dimer (from PQS)

Resolution:

1.76Å R-factor: 0.155

Authors:

Y.D.Devedjiev,A.N.Popov

Key ref:

Y.Devedjiev et al. (1997). X-ray structure at 1.76 A resolution of a polypeptide phospholipase A2 inhibitor. J Mol Biol, 266, 160-172. PubMed id: 9054978 DOI: 10.1006/jmbi.1996.0778

Date:

17-Dec-96 Release date: 24-Dec-97

Protein chain

P04084  (PA2HA_VIPAE) -  Acidic phospholipase A2 homolog vipoxin A chain from Vipera ammodytes meridionalis

Seq: 122 a.a.

Struc: 122 a.a.

DOI no: 10.1006/jmbi.1996.0778

J Mol Biol 266:160-172 (1997)

PubMed id: 9054978

X-ray structure at 1.76 A resolution of a polypeptide phospholipase A2 inhibitor.

Y.Devedjiev, A.Popov, B.Atanasov, H.D.Bartunik.

ABSTRACT

The high resolution crystal structure of a natural PLA2 inhibitor has been determined by Patterson search methods. In the heterodimeric, neurotoxic complex, vipoxin, isolated from the venom of Bulgarian viper, PLA2 inhibitor represents the non-toxic subunit. The model was refined to a crystallographic R-factor of 15.5% for data between 6 and 1.76 A resolution. The packing of the inhibitor in the crystal reveals close contacts between the molecules, which are symmetry-related by the 2-fold axes of the lattice. These pairs associate as a crystallographic dimer, stabilized by a set of interactions, including van der Waals contacts between residues from symmetry-related pairs, denoted as the recognition site and the recognition surface. Residues Ph3, Trp31 and Tyr119 represent the recognition site of inhibitor which possibly fits to the hydrophobic wall of the target PLA2. The topology of the inhibitor represents the PLA2 type of folding: three long helices and a beta-hairpin. Superposition of the structure of the inhibitor shows an almost complete overlap with different mammalian and viper PLA2 in the backbone and in the position of the sidechains of the residues that belong to the active centre and the hydrophobic wall. A "lock and key" mechanism of recognition of its native PLA2 in gland cells and other toxic PLA2 in vitro has been suggested. The mechanism includes complementary "head to tail" interactions between the recognition site of the inhibitor and a recognition surface located on the hydrophobic wall of the target PLA2. Having a high spatial homology with the PLA2 family of enzymes but opposing their action, the inhibitor from vipoxin presents an example of a divergent evolution of an ancient PLA2. The presence of a space for binding calcium in the inhibitor is believed to be a rudiment and proof of a common origin with PLA2.

Selected figure(s)

Figure 8.
Figure 8. Van-der-Waals contacts between the molecules of the inhibitor symmetry-related by the 2-fold axis of the lattice, that reveal the mechanism of lock and key recognition of the PLA[2] by the inhibitor of vipoxin. The residues involved in the recognition site: Trp31, Phe3 and Tyr119 are represented by balls-and-sticks as well as three water molecules located on the crystallographic axis. The residues forming the hydrophobic recognition surface are presented as hard spheres. White atoms belong to first symmetry-related molecule and the darkened atoms belong to the second molecule: (a) Trp31 cluster, (b) Phe3 cluster and (c) Tyr119 cluster. For details see the text. The drawing was created with MOLSCRIPT [Kraulis 1991].

Figure 9.
Figure 9. A view of a superposition of dimeric PLA[2] from Crotalus atrox venom on the crystallographic dimer of the PLA[2] inhibitor of vipoxin. Three water molecules found on the crystallographic 2-fold axis are represented by balls-and-sticks and the terminal residues are indicated by N and C. The drawing was created with MOLSCRIPT [Kraulis 1991].

The above figures are reprinted by permission from Elsevier: J Mol Biol (1997, 266, 160-172) copyright 1997.

Figures were selected by an automated process.