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Structure of KW‐2228, a tailored human granulocyte colony‐ stimulating factor with enhanced biological activity and stability
Author(s) -
Fujii Isao,
Nagahara Yoshitomo,
Yamasaki Motoo,
Yokoo Yoshiharu,
Itoh Seiga,
Hirayama Noriaki
Publication year - 1997
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(97)00538-3
Subject(s) - chemistry , helix (gastropod) , granulocyte colony stimulating factor , biological activity , biophysics , stereochemistry , biochemistry , biology , in vitro , genetics , chemotherapy , ecology , snail
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.