title: Structure of KW-2228, a tailored human granulocyte colony-stimulating factor with enhanced biological activity and stability.
abstract: 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.
authors.affiliation: Department of Biological Science and Technology, Tokai University, Numazu, Shizuoka, Japan.
authors.forename: I
authors.initials: I
authors.lastname: Fujii
authors.forename: Y
authors.initials: Y
authors.lastname: Nagahara
authors.forename: M
authors.initials: M
authors.lastname: Yamasaki
authors.forename: Y
authors.initials: Y
authors.lastname: Yokoo
authors.forename: S
authors.initials: S
authors.lastname: Itoh
authors.forename: N
authors.initials: N
authors.lastname: Hirayama
mesh_terms: 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
chemical_list: D004220:Disulfides; D016179:Granulocyte Colony-Stimulating Factor; C072115:nartograstim