PDBsum entry 2w2d

Hydrolase

PDB id

2w2d

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Contents

			Protein chains

					437 a.a. *


					424 a.a. *

			Ligands

					SO4 ×4


					GOL ×5


					ACT

			Metals

					_CL ×3


					_ZN ×2

			Waters ×308

* Residue conservation analysis

PDB id:

2w2d

Links
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Name:

Hydrolase

Title:

Crystal structure of a catalytically active, non-toxic endopeptidase derivative of clostridium botulinum toxin a

Structure:

Botulinum neurotoxin a light chain. Chain: a, c. Fragment: residues 1-442. Synonym: bontoxilysin-a. Engineered: yes. Botulinum neurotoxin a heavy chain. Chain: b, d. Fragment: residues 447-877. Synonym: bontoxilysin-a.

Source:

Clostridium botulinum. Organism_taxid: 1491. Expressed in: escherichia coli. Expression_system_taxid: 511693.

Resolution:

2.59Å

R-factor:

0.212

R-free:

0.253

Authors:

G.Masuyer,N.Thiyagarajan,P.L.James,P.M.H.Marks,J.A.Chaddock, K.R.Acharya

Key ref:

G.Masuyer et al. (2009). Crystal structure of a catalytically active, non-toxic endopeptidase derivative of Clostridium botulinum toxin A. Biochem Biophys Res Commun, 381, 50-53. PubMed id: 19351593

Date:

29-Oct-08

Release date:

24-Mar-09

PROCHECK

	Headers

	References

Protein chains

P0DPI1 (BXA1_CLOBH) - Botulinum neurotoxin type A from Clostridium botulinum (strain Hall / ATCC 3502 / NCTC 13319 / Type A)

Seq: Struc:

Seq: Struc:

Seq: Struc:					1296 a.a. 437 a.a.*

Protein chains

P0DPI1 (BXA1_CLOBH) - Botulinum neurotoxin type A from Clostridium botulinum (strain Hall / ATCC 3502 / NCTC 13319 / Type A)

Seq: Struc:

Seq: Struc:

Seq: Struc:					1296 a.a. 424 a.a.*

Key:

PfamA domain

Secondary structure

CATH domain

* PDB and UniProt seqs differ at 4 residue positions (black crosses)



		Enzyme reactions

Enzyme class:

Chains A, B, C, D: E.C.3.4.24.69 - bontoxilysin.

[IntEnz] [ExPASy] [KEGG] [BRENDA]

Reaction:

Limited hydrolysis of proteins of the neuroexocytosis apparatus, synaptobrevins, SNAP25 or syntaxin. No detected action on small molecule substrates.

Cofactor:

Zn(2+)

	Biochem Biophys Res Commun 381:50-53 (2009)
PubMed id: 19351593

Crystal structure of a catalytically active, non-toxic endopeptidase derivative of Clostridium botulinum toxin A.
G.Masuyer, N.Thiyagarajan, P.L.James, P.M.Marks, J.A.Chaddock, K.R.Acharya.

ABSTRACT

Botulinum neurotoxins (BoNTs) modulate cholinergic nerve terminals to result in neurotransmitter blockade. BoNTs consists of catalytic (LC), translocation (Hn) and cell-binding domains (Hc). The binding function of the Hc domain is essential for BoNTs to bind the neuronal cell membrane, therefore, removal of the Hc domain results in a product that retains the endopeptidase activity of the LC but is non-toxic. Thus, a molecule consisting of LC and Hn domains of BoNTs, termed LHn, is a suitable molecule for engineering novel therapeutics. The structure of LHA at 2.6 A reported here provides an understanding of the structural implications and challenges of engineering therapeutic molecules that combine functional properties of LHn of BoNTs with specific ligand partners to target different cell types.

Literature references that cite this PDB file's key reference

PubMed id

Reference

21078393

G.Masuyer, M.Beard, V.A.Cadd, J.A.Chaddock, and K.R.Acharya (2011).
Structure and activity of a functional derivative of Clostridium botulinum neurotoxin B.

J Struct Biol, 174, 52-57.

PDB code:

2xhl

20233039

M.Montal (2010).
Botulinum neurotoxin: a marvel of protein design.

Annu Rev Biochem, 79, 591-617.

The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.