PDBsum entry 1s0c

Toxin, hydrolase

PDB id: 1s0c

Contents

Protein chain

1287 a.a. *

Metals

_CA ×2

_ZN

Waters ×580

* Residue conservation analysis

PDB id:

1s0c

Name:

Toxin, hydrolase

Title:

Crystal structure of botulinum neurotoxin type b at ph 5.0

Structure:

Botulinum neurotoxin type b. Chain: a. Synonym: bont/b, bontoxilysin b. Ec: 3.4.24.69

Source:

Clostridium botulinum. Organism_taxid: 1491. Strain: type b

Resolution:

2.20Å R-factor: 0.204 R-free: 0.240

Authors:

S.Eswaramoorthy,D.Kumaran,J.Keller,S.Swaminathan

Key ref:

S.Eswaramoorthy et al. (2004). Role of metals in the biological activity of Clostridium botulinum neurotoxins. Biochemistry, 43, 2209-2216. PubMed id: 14979717 DOI: 10.1021/bi035844k

Date:

30-Dec-03 Release date: 16-Mar-04

Protein chain

P10844  (BXB_CLOBO) -  Botulinum neurotoxin type B from Clostridium botulinum

Seq: 1291 a.a.

Struc: 1287 a.a.

Enzyme reactions

• Enzyme class: E.C.3.4.24.69 - bontoxilysin.
• Reaction: Limited hydrolysis of proteins of the neuroexocytosis apparatus, synaptobrevins, SNAP25 or syntaxin. No detected action on small molecule substrates.
• Cofactor: Zn(2+)

DOI no: 10.1021/bi035844k

Biochemistry 43:2209-2216 (2004)

PubMed id: 14979717

Role of metals in the biological activity of Clostridium botulinum neurotoxins.

S.Eswaramoorthy, D.Kumaran, J.Keller, S.Swaminathan.

ABSTRACT

Clostridium botulinum neurotoxins are the most potent toxins to humans and cause paralysis by blocking neurotransmitter release at the presynaptic nerve terminals. The toxicity involves four steps, viz., binding to neuronal cells, internalization, translocation, and catalytic activity. While the catalytic activity is a zinc endopeptidase activity on the SNARE complex proteins, the translocation is believed to be a pH-dependent process allowing the translocation domain to change its conformation to penetrate the endosomal membrane. Here, we report the crystal structures of botulinum neurotoxin type B at various pHs and of an apo form of the neurotoxin, and discuss the role of metal ions and the effect of pH variation in the biological activity. Except for the perturbation of a few side chains, the conformation of the catalytic domain is unchanged in the zinc-depleted apotoxin, suggesting that zinc's role is catalytic. We have also identified two calcium ions in the molecule and present biochemical evidence to show that they play a role in the translocation of the light chain through the membrane.