PDBsum entry 2qn0

Toxin

PDB id: 2qn0

Contents

Protein chain

429 a.a. *

Metals

_ZN

Waters ×613

* Residue conservation analysis

PDB id:

2qn0

Name:

Toxin

Title:

Structure of botulinum neurotoxin serotype c1 light chain protease

Structure:

Neurotoxin. Chain: a. Fragment: light chain (residues:1-427). Synonym: typE C neurotoxin. Engineered: yes

Source:

Clostridium botulinum. Organism_taxid: 1491. Gene: bont/c. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

1.75Å R-factor: 0.188 R-free: 0.205

Authors:

R.Jin,S.Sikorra,C.M.Stegmann,A.Pich,T.Binz,A.T.Brunger

Key ref:

R.Jin et al. (2007). Structural and biochemical studies of botulinum neurotoxin serotype C1 light chain protease: implications for dual substrate specificity. Biochemistry, 46, 10685-10693. PubMed id: 17718519

Date:

17-Jul-07 Release date: 11-Sep-07

Protein chain

P18640  (BXC_CBCP) -  Botulinum neurotoxin type C from Clostridium botulinum C phage

Seq: 1291 a.a.

Struc: 429 a.a.*

* PDB and UniProt seqs differ at 3 residue positions (black crosses)

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+)

Biochemistry 46:10685-10693 (2007)

PubMed id: 17718519

Structural and biochemical studies of botulinum neurotoxin serotype C1 light chain protease: implications for dual substrate specificity.

R.Jin, S.Sikorra, C.M.Stegmann, A.Pich, T.Binz, A.T.Brunger.

ABSTRACT

Clostridial neurotoxins are the causative agents of the neuroparalytic disease botulism and tetanus. They block neurotransmitter release through specific proteolysis of one of the three soluble N-ethylmaleimide-sensitive-factor attachment protein receptors (SNAREs) SNAP-25, syntaxin, and synaptobrevin, which constitute part of the synaptic vesicle fusion machinery. The catalytic component of the clostridial neurotoxins is their light chain (LC), a Zn2+ endopeptidase. There are seven structurally and functionally related botulinum neurotoxins (BoNTs), termed serotype A to G, and tetanus neurotoxin (TeNT). Each of them exhibits unique specificity for their target SNAREs and peptide bond(s) they cleave. The mechanisms of action for substrate recognition and target cleavage are largely unknown. Here, we report structural and biochemical studies of BoNT/C1-LC, which is unique among BoNTs in that it exhibits dual specificity toward both syntaxin and SNAP-25. A distinct pocket (S1') near the active site likely achieves the correct register for the cleavage site by only allowing Ala as the P1' residue for both SNAP-25 and syntaxin. Mutations of this SNAP-25 residue dramatically reduce enzymatic activity. The remote alpha-exosite that was previously identified in the complex of BoNT/A-LC and SNAP-25 is structurally conserved in BoNT/C1. However, mutagenesis experiments show that the alpha-exosite of BoNT/C1 plays a less stringent role in substrate discrimination in comparison to that of BoNT/A, which could account for its dual substrate specificity.