Solution structures of long-acting insulin analogues and their complexes with albumin.

Ryberg LA, Sønderby P, Barrientos F, Bukrinski JT, Peters GHJ, Harris P, Acta Crystallogr D Struct Biol 75(Pt 3):272-282 (2019) Europe PMC

SASDEZ5 – Albumin-insulin detemir 2:12 complex, P2 symmetry

Human Albumin (Recombumin(R) Alpha, Albumedix Ltd.)
Insulin detemir (Levemir(R), Novo Nordisk A/S)
MWexperimental 208 kDa
MWexpected 137 kDa
VPorod 309 nm3
log I(s) 1.50×10-1 1.50×10-2 1.50×10-3 1.50×10-4
Human Albumin (Recombumin(R) Alpha, Albumedix Ltd.) Insulin detemir (Levemir(R), Novo Nordisk A/S) small angle scattering data  s, nm-1
ln I(s)
Human Albumin (Recombumin(R) Alpha, Albumedix Ltd.) Insulin detemir (Levemir(R), Novo Nordisk A/S) Guinier plot ln 1.50×10-1 Rg: 5.4 nm 0 (5.4 nm)-2 s2
(sRg)2I(s)/I(0)
Human Albumin (Recombumin(R) Alpha, Albumedix Ltd.) Insulin detemir (Levemir(R), Novo Nordisk A/S) Kratky plot 1.104 0 √3 sRg
p(r)
Human Albumin (Recombumin(R) Alpha, Albumedix Ltd.) Insulin detemir (Levemir(R), Novo Nordisk A/S) pair distance distribution function Rg: 5.7 nm 0 Dmax: 19.5 nm

Data validation

Fits and models

log I(s)
 s, nm-1
Human Albumin (Recombumin(R) Alpha, Albumedix Ltd.) Insulin detemir (Levemir(R), Novo Nordisk A/S) SASREF CV model
log I(s)
 s, nm-1
Human Albumin (Recombumin(R) Alpha, Albumedix Ltd.) Insulin detemir (Levemir(R), Novo Nordisk A/S) DAMMIN model
Synchrotron SAXS data from solutions of Albumin-insulin detemir (2:12 complex, P2 symmetry) in 8.8 mM Na2HPO4, 10.6 mM m-cresol, 12.2 mM phenol, 140.9 mM glycerol, 56.9 mM NaCl, pH 7.4 were collected on the I911-4 beam line at the MAX IV storage ring (Lund, Sweden) using a Dectris Pilatus 1M detector at a sample-detector distance of 2.0 m and at a wavelength of λ = 0.091 nm (l(s) vs s, where s = 4πsinθ/λ, and 2θ is the scattering angle). One solute concentration of 15.60 mg/ml was measured at 20°C. Four successive 30 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.

Storage temperature = UNKNOWN

Human Albumin (Recombumin(R) Alpha, Albumedix Ltd.)
Mol. type   Protein
Olig. state   Monomer
Mon. MW   66.5 kDa
 
UniProt   P02768 (25-609)
Sequence   FASTA
 
Insulin detemir (Levemir(R), Novo Nordisk A/S)
Mol. type   Protein
Olig. state   Dodecamer
Mon. MW   5.9 kDa
 
UniProt   P01308
Sequence   FASTA
 
PDB ID   1BJ5
 
PDB ID   1TRZ