PDBsum entry: 1bun

Toxin

PDB id: 1bun

Contents

Protein chains

120 a.a. *

61 a.a. *

Metals

_NA ×2

Waters ×81

* Residue conservation analysis

PDB id:

1bun

Name:

Toxin

Title:

Structure of beta2-bungarotoxin: potassium channel binding by kunitz modules and targeted phospholipase action

Structure:

Beta2-bungarotoxin. Chain: a. Synonym: phosphatide acyl-hydrolase, phosphatidylcholine 2- acylhydrolase. Other_details: numerous natural isoforms, this is the beta2 isoform. Beta2-bungarotoxin. Chain: b. Synonym: phosphatide acyl-hydrolase, phosphatidylcholine 2-

Source:

Bungarus multicinctus. Many-banded krait. Organism_taxid: 8616. Tissue: venom. Tissue: venom

Biol. unit:

Hetero-Dimer (from PQS)

Resolution:

2.45Å R-factor: 0.193 R-free: 0.281

Authors:

P.D.Kwong,N.Q.Mcdonald,P.B.Sigler,W.A.Hendrickson

Key ref:

P.D.Kwong et al. (1995). Structure of beta 2-bungarotoxin: potassium channel binding by Kunitz modules and targeted phospholipase action. Structure, 3, 1109-1119. PubMed id: 8590005 DOI: 10.1016/S0969-2126(01)00246-5

Date:

15-Oct-95 Release date: 03-Apr-96

Protein chain

P00617  (PA21B_BUNMU) -  Phospholipase A2, beta bungarotoxin A1 chain

Seq: 147 a.a.

Struc: 120 a.a.*

Protein chain

P00989  (IVBI2_BUNMU) -  Beta-bungarotoxin B2 chain

Seq: 85 a.a.

Struc: 61 a.a.

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

Enzyme reactions

• Enzyme class: Chain A: E.C.3.1.1.4 - Phospholipase A(2).
• Reaction: Phosphatidylcholine + H₂O = 1-acylglycerophosphocholine + a carboxylate
• Cofactor: Calcium

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

 Gene Ontology (GO) functional annotation 

• Cellular component: extracellular region (2 terms)
• Biological process: lipid catabolic process (4 terms)
• Biochemical function: hydrolase activity (7 terms)

reference

DOI no: 10.1016/S0969-2126(01)00246-5

Structure 3:1109-1119 (1995)

PubMed id: 8590005

Structure of beta 2-bungarotoxin: potassium channel binding by Kunitz modules and targeted phospholipase action.

P.D.Kwong, N.Q.McDonald, P.B.Sigler, W.A.Hendrickson.

ABSTRACT

BACKGROUND: beta-bungarotoxin is a heterodimeric neurotoxin consisting of a phospholipase subunit linked by a disulfide bond to a K+ channel binding subunit which is a member of the Kunitz protease inhibitor superfamily. Toxicity, characterized by blockage of neural transmission, is achieved by the lipolytic action of the phospholipase targeted to the presynaptic membrane by the Kunitz module. RESULTS: The crystal structure at 2.45 A resolution suggests that the ion channel binding region of the Kunitz subunit is at the opposite end of the module from the loop typically involved in protease binding. Analysis of the phospholipase subunit reveals a partially occluded substrate-binding surface and reduced hydrophobicity. CONCLUSIONS: Molecular recognition by this Kunitz module appears to diverge considerably from more conventional superfamily members. The ion channel binding region identified here may mimic the regulatory interaction of endogenous neuropeptides. Adaptations of the phospholipase subunit make it uniquely suited to targeting and explain the remarkable ability of the toxin to avoid binding to non-target membranes. Insight into the mechanism of beta-bungarotoxin gained here may lead to the development of therapeutic strategies against not only pathological cells, but also enveloped viruses.

Selected figure(s)

Figure 6.
Figure 6. Electrostatic potential at the molecular surface of β[2]-bungarotoxin. Blue represents positive potential, red negative, and white neutral. The positions of selected features are highlighted. Figure 6. Electrostatic potential at the molecular surface of β[2]-bungarotoxin. Blue represents positive potential, red negative, and white neutral. The positions of selected features are highlighted. (Computed with GRASP [[3]56] at neutral pH.)

Figure 7.
Figure 7. Chemical and physical properties of the phospholipase surface proximal to the substrate-binding region. (a) Hydrophobic area and proximal area of the surface within 7.5 å of the substrate acyl chains. Shown are (•) toxic phospholipases, (○) non-toxic phospholipases from structures without substrate, and (□) non-toxic phospholipases from structures of substrate complexes. ‘N’ and ‘B’ label notexin and β[2]-bungarotoxin respectively. (b) Phospholipase molecular surface colored by the physical properties of the underlying atoms: hydrophobic (green); charged (purple); polar (white). Portions of the surface that are >7.5 å from the substrate acyl chairs are colored orange. The surfaces depicted are (from left to right) β[2]-bungarotoxin, notexin, and the phospholipases from cobra (Naja naja atra class I), rattlesnake (Crotalus atrox class II) and honeybee (Apis mellifera insect). Figure 7. Chemical and physical properties of the phospholipase surface proximal to the substrate-binding region. (a) Hydrophobic area and proximal area of the surface within 7.5 å of the substrate acyl chains. Shown are (•) toxic phospholipases, (○) non-toxic phospholipases from structures without substrate, and (□) non-toxic phospholipases from structures of substrate complexes. ‘N’ and ‘B’ label notexin and β[2]-bungarotoxin respectively. (b) Phospholipase molecular surface colored by the physical properties of the underlying atoms: hydrophobic (green); charged (purple); polar (white). Portions of the surface that are >7.5 å from the substrate acyl chairs are colored orange. The surfaces depicted are (from left to right) β[2]-bungarotoxin, notexin, and the phospholipases from cobra (Naja naja atra class I), rattlesnake (Crotalus atrox class II) and honeybee (Apis mellifera insect). (Figure made with GRASP [[4]56].)

The above figures are reprinted by permission from Cell Press: Structure (1995, 3, 1109-1119) copyright 1995.

Figures were selected by the author.