1H, 13C and 15N backbone assignments of cyclophilin when bound to cyclosporin A (CsA) and preliminary structural characterization of the CsA binding site.
The backbone 1H, 13C and 15N chemical shifts of cyclophilin (CyP) when bound to cyclosporin A (CsA) have been assigned from heteronuclear two- and three-dimensional NMR experiments involving selectively 15N- and uniformly 15N- and 15N,13C-labeled cyclophilin. From an analysis of the 1H and 15N chemical shifts of CyP that change upon binding to CsA and from CyP/CsA NOEs, we have determined the regions of cyclophilin involved in binding to CsA.
Neri
P
P
Pharmaceutical Discovery Division, Abbott Laboratories, Abbott Park, IL 60064.
Meadows
R
R
Gemmecker
G
G
Olejniczak
E
E
Nettesheim
D
D
Logan
T
T
Simmer
R
R
Helfrich
R
R
Holzman
T
T
Severin
J
J
D000591:Amino Acid Isomerases / Q000737:chemistry* / Q000378:metabolism; D000595:Amino Acid Sequence; D001665:Binding Sites; D002247:Carbon Isotopes; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism; D003001:Cloning, Molecular; D016572:Cyclosporine / Q000378:metabolism*; D006801:Humans; D006859:Hydrogen; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009584:Nitrogen; D019696:Peptidylprolyl Isomerase; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism
D002247:Carbon Isotopes; D002352:Carrier Proteins; D011994:Recombinant Proteins; D006859:Hydrogen; D016572:Cyclosporine; D000591:Amino Acid Isomerases; D019696:Peptidylprolyl Isomerase; D009584:Nitrogen