The influence of pH alteration and pharmacological modulators of adenylate cyclase system on human serum albumin conformation.
The report describes the results of a study the effect of pH and binding of six physiologically active compounds (isoproterenol, yohimbine, theophylline, propranolol, clonidine and carbachol) on the molecular structure of human serum albumin (HSA) using dynamic light scattering. It was found that the albumin globule had the most compact configuration (Stokes diameter 59-62A) at physiological pH 7.4. The changes in pH both increased to 8.0 and decreased to 5.4, resulting in the growth of globule size to 72-81A. At acidic shift of pH an additional peak arose in the correlation spectra. This peak was caused by the light scattering on the structures with the Stokes diameters of 29-37A, which conformed to the sizes of the albumin subdomains. The additional peak was not displayed at basic shift of pH. The interaction with propranolol, clonidine and carbachol, which hinder adenylate cyclase (AdC) signaling system of a cell, initiated structural rearrangements similar to acidic transitions. Isoproterenol, yohimbine and theophylline, which activate AdC, caused the conformational changes of HSA similar to basic transitions.
Luik
A I
AI
Department of Biomedical Research, Institute of Bioorganic Chemistry and Petrochemistry, National Academy of Sciences of Ukraine, Kyiv. luik@bioorganic.kiev.ua
Naboka
Y N
YN
Mogilevich
S E
SE
Hushcha
T O
TO
Mischenko
N I
NI
D000262:Adenylyl Cyclases; D002217:Carbachol / Q000378:metabolism / Q000494:pharmacology*; D003000:Clonidine / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007545:Isoproterenol / Q000378:metabolism / Q000494:pharmacology*; D011433:Propranolol / Q000378:metabolism / Q000494:pharmacology*; D011487:Protein Conformation; D012709:Serum Albumin / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D013806:Theophylline / Q000378:metabolism / Q000494:pharmacology*; D015016:Yohimbine / Q000378:metabolism / Q000494:pharmacology*
D012709:Serum Albumin; D015016:Yohimbine; D002217:Carbachol; D011433:Propranolol; D013806:Theophylline; D000262:Adenylyl Cyclases; D007545:Isoproterenol; D003000:Clonidine