Structure of KW‐2228, a tailored human granulocyte colony‐ stimulating factor with enhanced biological activity and stability

FEBS Letters

Fujii, Isao²  Yokoo, Yoshiharu¹  Yamasaki, Motoo¹  Itoh, Seiga¹  Hirayama, Noriaki²  Nagahara, Yoshitomo¹ 

[1] Tokyo Research Laboratories, Kyowa Hakko Kogyo Co. Ltd., 3-6-6 Asahimachi, Machida, Tokyo 194, Japan;Department of Biological Science and Technology, Tokai University, 317 Nishino, Numazu, Shizuoka 410-03, Japan

关键词: Granulocyte colony-stimulating factor;    Tailored protein;    Conformation;    X-ray crystallography;    Structure-activity relationship;    Lymphokine;   

DOI  :  10.1016/S0014-5793(97)00538-3

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 Å resolution crystal structure of KW-2228 unambiguously revealed a four-α-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.

【 授权许可】

Unknown