STRUCTURE OF KW-2228, A TAILORED HUMAN GRANULOCYTE-COLONY-STIMULATINGFACTOR 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 Angstrom resolution crystal structure of KW-2228 unambiguously revealed a four-cc-helix bundle mo tif with up-up-down-down connectivity. The structures of long overhand loops connecting the helices and the N-terminus have been definitivel y determined. The present analysis has clearly revealed that substitut ed 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 activi ty and stability. (C) 1997 Federation of European Biochemical Societie s.