Stabilization of the FK506 binding protein by ligand binding.
Although the rotamase activity of the FK506 binding protein is inhibited by ligand binding, it is hypothesized that the ligand/protein complex itself may be responsible for the immunosuppressive effects of FK506. We have therefore examined the structure of the FK506 binding protein in the presence of an analog of FK506 (FK520) by a combination of fluorescence, CD, FTIR and calorimetry. While only small changes in the overall structure of the protein may be induced by ligand, a large change in thermal stability of the binding protein is observed.
Marquis-Omer
D
D
Department of Pharmaceutical Research, Merck Sharp & Dohme Research Laboratories, West Point, PA 19486.
Sanyal
G
G
Volkin
D B
DB
Marcy
A I
AI
Chan
H K
HK
Ryan
J A
JA
Middaugh
C R
CR
D000900:Anti-Bacterial Agents / Q000737:chemistry; D002151:Calorimetry; D002352:Carrier Proteins / Q000737:chemistry*; D002942:Circular Dichroism; D005583:Fourier Analysis; D006801:Humans; D007166:Immunosuppressive Agents / Q000737:chemistry*; D008024:Ligands; D010880:Piperidines / Q000737:chemistry*; D011994:Recombinant Proteins / Q000737:chemistry; D013050:Spectrometry, Fluorescence; D013055:Spectrophotometry, Infrared; D013329:Structure-Activity Relationship; D016559:Tacrolimus / Q000031:analogs & derivatives; D022021:Tacrolimus Binding Proteins; D013696:Temperature
D000900:Anti-Bacterial Agents; D002352:Carrier Proteins; D007166:Immunosuppressive Agents; D008024:Ligands; D010880:Piperidines; D011994:Recombinant Proteins; C058028:immunomycin; D022021:Tacrolimus Binding Proteins; D016559:Tacrolimus