Review of recent developments in the molecular characterization of recombinant alfa interferons on the 40th anniversary of the discovery of interferon.
Recombinant alfa interferons (IFN-alpha s) are approved worldwide for the treatment of a variety of cancers and diseases of virologic origin. A series of recent advances in the molecular characterization of recombinant IFN-alpha s have allowed the determination of the three-dimensional IFN-alpha 2b structure by high-resolution x-ray crystallography. We review here recent developments in our understanding of the molecular and physicochemical properties of recombinant IFN-alpha, including our current state of knowledge of the IFN-alpha gene family and the multiple species of human leukocyte IFN. Based on the reported three-dimensional structure of IFN-alpha 2b, we propose a molecular model for the IFN-alpha 2b receptor complex and predict models for the naturally occurring subtypes IFN-alpha 1 and IFN-alpha 8, as well as the synthetic, non-naturally occurring consensus IFN. Such models provide molecular insights into the mechanism of action of IFN-alpha.
Walter
M R
MR
Department of Microbiology, University of Alabama at Birmingham 35294-0005, USA.
Bordens
R
R
Nagabhushan
T L
TL
Williams
B R
BR
Herberman
R B
RB
Dinarello
C A
CA
Borden
E C
EC
Trotta
P P
PP
Pestka
S
S
Pfeffer
L M
LM
D006801:Humans; D007370:Interferon Type I / Q000737:chemistry* / Q000627:therapeutic use*; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000737:chemistry / Q000235:genetics; D008958:Models, Molecular; D009369:Neoplasms / Q000188:drug therapy*; D011487:Protein Conformation; D017471:Receptors, Interferon / Q000737:chemistry; D011994:Recombinant Proteins; D014777:Virus Diseases / Q000188:drug therapy*
D007370:Interferon Type I; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D017471:Receptors, Interferon; D011994:Recombinant Proteins