Structure of KW-2228, a tailored human granulocyte colony-stimulating factor with enhanced biological activity and stability.
KW-2228 is a tailored human granulocyte colony-stimulating factor (hG-CSF) which has more potent granulopoietic activity and is more stable than wild-type hG-CSF. Analysis of the 2.3 A resolution crystal structure of KW-2228 unambiguously revealed a four-alpha-helix bundle motif with up-up-down-down connectivity. The structures of long overhand loops connecting the helices and the N-terminus have been definitively determined. The present analysis has clearly revealed that substituted residues play important roles in fastening a long overhand loop to the N- and C-termini to fix the conformation. This conformation should be responsible for a substantial enhancement of the biological activity and stability.
Fujii
I
I
Department of Biological Science and Technology, Tokai University, Numazu, Shizuoka, Japan.
Nagahara
Y
Y
Yamasaki
M
M
Yokoo
Y
Y
Itoh
S
S
Hirayama
N
N
D018360:Crystallography, X-Ray; D004220:Disulfides; D016179:Granulocyte Colony-Stimulating Factor / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D008958:Models, Molecular; D017433:Protein Structure, Secondary; D013329:Structure-Activity Relationship
D004220:Disulfides; D016179:Granulocyte Colony-Stimulating Factor; C072115:nartograstim