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

SASDVM6 – Dipeptidyl peptidase 9 (DPP9) with compound 42

Isoform 1 of Dipeptidyl peptidase 9
MWexperimental 199 kDa
MWexpected 198 kDa
VPorod 274 nm3
log I(s) 2.73×102 2.73×101 2.73×100 2.73×10-1
Isoform 1 of Dipeptidyl peptidase 9 small angle scattering data  s, nm-1
ln I(s)
Isoform 1 of Dipeptidyl peptidase 9 Guinier plot ln 2.74×102 Rg: 4.1 nm 0 (4.1 nm)-2 s2
(sRg)2I(s)/I(0)
Isoform 1 of Dipeptidyl peptidase 9 Kratky plot 1.104 0 3 sRg
p(r)
Isoform 1 of Dipeptidyl peptidase 9 pair distance distribution function Rg: 4.1 nm 0 Dmax: 12.5 nm

Data validation


Fits and models


log I(s)
 s, nm-1
Isoform 1 of Dipeptidyl peptidase 9 BILBOMD model

log I(s)
 s, nm-1

Synchrotron SAXS data from solutions of DPP9 with compound 42 in 25 mM HEPES, 150 mM NaCl, 2 mM DTT, pH 7.5 were collected on the BM29 beam line at the ESRF (Grenoble, France) using a Pilatus3 2M detector at a sample-detector distance of 2.9 m and at a wavelength of λ = 0.103 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 50.00 μl sample at 12 mg/ml was injected at a 0.20 ml/min flow rate onto a Shodex KW404-4F column at 20°C. 750 successive 2 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 9
Mol. type   Protein
Organism   Homo sapiens
Olig. state   Dimer
Mon. MW   99.1 kDa
 
UniProt   Q86TI2-1 (1-863)
Sequence   FASTA