Computational study of DPP8 and DPP9: fundamental insights and inhibitor design

Olivier Beyens, Yann Sterckx, University of Antwerp PhD thesis c:irua:209673 (2024) URL

SASDVJ6 – apo Dipeptidyl peptidase 8 (DPP8 apo)

Isoform 1 of Dipeptidyl peptidase 8
MWexperimental 206 kDa
MWexpected 208 kDa
VPorod 271 nm3
log I(s) 1.72×10-1 1.72×10-2 1.72×10-3 1.72×10-4
Isoform 1 of Dipeptidyl peptidase 8 small angle scattering data  s, nm-1
ln I(s)
Isoform 1 of Dipeptidyl peptidase 8 Guinier plot ln 1.72×10-1 Rg: 4.2 nm 0 (4.2 nm)-2 s2
(sRg)2I(s)/I(0)
Isoform 1 of Dipeptidyl peptidase 8 Kratky plot 1.104 0 √3 sRg
p(r)
Isoform 1 of Dipeptidyl peptidase 8 pair distance distribution function Rg: 4.2 nm 0 Dmax: 13.6 nm

Data validation

Fits and models

log I(s)
 s, nm-1
Isoform 1 of Dipeptidyl peptidase 8 BILBOMD model
log I(s)
 s, nm-1
Synchrotron SAXS data from solutions of DPP8 apo in 25 mM HEPES, 150 mM NaCl, 2 mM DTT, pH 7.5 were collected on the SWING beam line at SOLEIL (Saint-Aubin, France) using a Eiger 4M detector at a sample-detector distance of 2 m and at a wavelength of λ = 0.099 nm (I(s) vs s, where s = 4πsinθ/λ, and 2θ is the scattering angle). In-line size-exclusion chromatography (SEC) SAS was employed. The SEC parameters were as follows: A 40.00 μl sample at 11.9 mg/ml was injected at a 0.20 ml/min flow rate onto a Shodex KW404-4F column at 20°C. 870 successive 0.990 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.

Isoform 1 of Dipeptidyl peptidase 8
Mol. type   Protein
Organism   Homo sapiens
Olig. state   Dimer
Mon. MW   104.2 kDa
 
UniProt   Q6V1X1-1 (1-898)
Sequence   FASTA