PDBsum entry 1jlt

Hydrolase

PDB id: 1jlt

Contents

Protein chains

122 a.a. *

122 a.a. *

Ligands

MRD

MPD

Waters ×320

* Residue conservation analysis

PDB id:

1jlt

Name:

Hydrolase

Title:

Vipoxin complex

Structure:

Phospholipase a2 inhibitor. Chain: a. Phospholipase a2. Chain: b. Synonym: vipoxin. Ec: 3.1.1.4

Source:

Vipera ammodytes ammodytes. Western sand viper. Organism_taxid: 8705. Strain: ammodytes. Other_details: sequence homology between phospholipase and its inhibitor in snake venom. The primary structure of phospholipase a2 of vipoxin from the venom of the bulgarian viper (vipera ammodytes ammodytes, serpentes)

Biol. unit:

Dimer (from PQS)

Resolution:

1.40Å R-factor: 0.182 R-free: 0.195

Authors:

S.Banumathi,K.R.Rajashankar,C.Notzel,B.Aleksiev,T.P.Singh,N.Genov, C.Betzel

Key ref:

S.Banumathi et al. (2001). Structure of the neurotoxic complex vipoxin at 1.4 A resolution. Acta Crystallogr D Biol Crystallogr, 57, 1552-1559. PubMed id: 11679719 DOI: 10.1107/S0907444901013543

Date:

16-Jul-01 Release date: 31-Oct-01

Protein chain

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

Seq: 122 a.a.

Struc: 122 a.a.*

Protein chain

P14420  (PA2B_VIPAE) -  Basic phospholipase A2 vipoxin B chain from Vipera ammodytes meridionalis

Seq: 122 a.a.

Struc: 122 a.a.

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: Chain B: 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: 10.1107/S0907444901013543

Acta Crystallogr D Biol Crystallogr 57:1552-1559 (2001)

PubMed id: 11679719

Structure of the neurotoxic complex vipoxin at 1.4 A resolution.

S.Banumathi, K.R.Rajashankar, C.Nötzel, B.Aleksiev, T.P.Singh, N.Genov, C.Betzel.

ABSTRACT

Vipoxin is a neurotoxic postsynaptic heterodimeric complex from the venom of Vipera ammodytes meridionalis, the most toxic snake in Europe. It consists of a basic and highly toxic phospholipase A(2) and an acidic non-toxic protein inhibitor. The two polypeptide chains have the same chain length and share 62% amino-acid identity. Vipoxin is a unique example of evolution of the catalytic and toxic phospholipase A(2) functions into inhibitory and non-toxic functions. The crystal structure of the complex has been determined by the molecular-replacement method and refined to 1.4 A resolution to an R factor of 18.2%. The complex formation decreases the accessible surface area of the two subunits by approximately 1480 A(2), which results in a reduction of toxicity and catalytic activity. The catalytic and substrate-binding sites of the vipoxin phospholipase A(2) are identical or similar to those of other group I/II enzymes. Two 2-methyl-2,4-pentanediol molecules are present in the hydrophobic channel close to the active site. The two subunits lack calcium ions. The negatively charged Asp49 of the phospholipase A(2), which participates in the Ca(2+)-binding sites of other snake-venom phospholipase A(2)s, is neutralized by the side chain of Lys69 from the inhibitor. Attempts have been made to identify the toxicity region and to explain the reduced catalytic activity and toxicity of the phospholipase A(2) subunit.

Selected figure(s)

Figure 1.
Figure 1 Ribbon representation of the PLA[2]. The disulfide bridges and active-site residues are shown as ball-and-stick models. Secondary-structure regions and the Ca^2+-binding region as well as regions of pharmacological functions are labelled. Additionally, conserved and invariant residues found in approximately 200 sequences of PLA[2]s (Danse et al., 1997[Danse, J. M., Gasparini, S. & Menez, A. (1997). Venom Phospholipase A2 Enzymes: Structure, Function and Mechanism, edited by R. M. Kini, pp. 29-72. Chichester: John Wiley & Sons.]) are labelled at their C^ position.

Figure 2.
Figure 2 Stereo figure showing the electron density in the active-site region with superimposed amino acids, solvent water and one MPD molecule. All hydrogen bonds and interactions are indicated with their distances.

The above figures are reprinted by permission from the IUCr: Acta Crystallogr D Biol Crystallogr (2001, 57, 1552-1559) copyright 2001.

Figures were selected by an automated process.