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

SASDEW5 – Albumin-insulin detemir 1:6 complex, binding in Südlow's Site II

Insulin detemir (Levemir(R), Novo Nordisk A/S)
Human Albumin (Recombumin(R) Alpha, Albumedix Ltd.)
MWexperimental 102 kDa
MWexpected 102 kDa
VPorod 162 nm3
log I(s) 7.40×10-2 7.40×10-3 7.40×10-4 7.40×10-5
Insulin detemir (Levemir(R), Novo Nordisk A/S) Human Albumin (Recombumin(R) Alpha, Albumedix Ltd.) small angle scattering data  s, nm-1
ln I(s)
Insulin detemir (Levemir(R), Novo Nordisk A/S) Human Albumin (Recombumin(R) Alpha, Albumedix Ltd.) Guinier plot ln 7.40×10-2 Rg: 3.5 nm 0 (3.5 nm)-2 s2
(sRg)2I(s)/I(0)
Insulin detemir (Levemir(R), Novo Nordisk A/S) Human Albumin (Recombumin(R) Alpha, Albumedix Ltd.) Kratky plot 1.104 0 √3 sRg
p(r)
Insulin detemir (Levemir(R), Novo Nordisk A/S) Human Albumin (Recombumin(R) Alpha, Albumedix Ltd.) pair distance distribution function Rg: 3.6 nm 0 Dmax: 13.0 nm

Data validation

Fits and models

log I(s)
 s, nm-1
Insulin detemir (Levemir(R), Novo Nordisk A/S) Human Albumin (Recombumin(R) Alpha, Albumedix Ltd.) SASREF CV model
log I(s)
 s, nm-1
Insulin detemir (Levemir(R), Novo Nordisk A/S) Human Albumin (Recombumin(R) Alpha, Albumedix Ltd.) DAMMIF model
Synchrotron SAXS data from solutions of Albumin-insulin detemir (1:6 complex, binding in Südlow's Site II) in 6.9 mM Na2HPO4, 11.9 mM m-cresol, 13.7 mM phenol, 157.3 mM glycerol, 38.5 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 8.50 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

Insulin detemir (Levemir(R), Novo Nordisk A/S)
Mol. type   Protein
Olig. state   Hexamer
Mon. MW   5.9 kDa
 
UniProt   P01308 (25-110)
Sequence   FASTA
 
Human Albumin (Recombumin(R) Alpha, Albumedix Ltd.)
Mol. type   Protein
Olig. state   Monomer
Mon. MW   66.5 kDa
 
UniProt   P02768 (25-609)
Sequence   FASTA
 
PDB ID   1BJ5
 
PDB ID   1TRZ