Covalent inhibition of hAChE by organophosphates causes homodimer dissociation through long-range allosteric effects

Donald Blumenthal.

SASDL92 – Human acetylcholinesterase, covalently bound to paraoxon

acetylcholinesterase
acetylcholinesterase
MWexperimental 91 kDa
MWexpected 181 kDa
VPorod 142 nm3
log I(s) 6.03×102 6.03×101 6.03×100 6.03×10-1
acetylcholinesterase acetylcholinesterase small angle scattering data  s, nm-1
ln I(s)
acetylcholinesterase acetylcholinesterase Guinier plot ln 6.04×102 Rg: 3.4 nm 0 (3.4 nm)-2 s2
(sRg)2I(s)/I(0)
acetylcholinesterase acetylcholinesterase Kratky plot 1.104 0 3 sRg
p(r)
acetylcholinesterase acetylcholinesterase pair distance distribution function Rg: 3.6 nm 0 Dmax: 12 nm

Data validation


Fits and models


log I(s)
 s, nm-1
acetylcholinesterase acetylcholinesterase PDB model
acetylcholinesterase acetylcholinesterase PDB model

Synchrotron SAXS data from solutions of Human acetylcholinesterase, covalently bound to paraoxon in 50 mM Tris/HCl, 100 mM NaCl, pH 7.4 were collected on the BL4-2 beam line at the Stanford Synchrotron Radiation Lightsource (SSRL) storage ring (Menlo Park, CA, USA) using a Rayonix MX225-HE detector (I(s) vs s, where s = 4πsinθ/λ, and 2θ is the scattering angle). One solute concentration of 2.00 mg/ml was measured at 22°C. 10 successive 1 second frames were collected. The data were normalized to the intensity of the transmitted beam and radially averaged; the scattering of the solvent-blank was subtracted.

The estimated experimental MW and shape of the PDDF indicate this sample represents a mixture of homodimer and monomer. X-ray wavelength: UNKNOWN.

acetylcholinesterase (AChE)
Mol. type   Protein
Organism   Homo sapiens
Olig. state   Dimer
Mon. MW   60.2 kDa
 
UniProt   P22303-1 (32-578)
Sequence   FASTA
 
acetylcholinesterase (AChE)
Mol. type   Protein
Organism   Homo sapiens
Olig. state   Monomer
Mon. MW   60.2 kDa
 
UniProt   P22303-1 (32-578)
Sequence   FASTA
 
PDB code   6O4X
 
PDB code   6O4X