CARNOSINE BINDING - CHARACTERIZATION OF STERIC AND CHARGE REQUIREMENTS FOR LIGAND RECOGNITION

被引:19
作者
BROWN, CE
MARGOLIS, FL
WILLIAMS, TH
PITCHER, RG
ELGAR, GJ
机构
[1] ROCHE INST MOLEC BIOL,NUTLEY,NJ 07110
[2] HOFFMANN LA ROCHE INC,DEPT CHEM RES,NUTLEY,NJ 07110
关键词
D O I
10.1016/0003-9861(79)90060-2
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The steric and charge requirements for binding of l-carnosine (β-alanyl-l-histidine) by bovine serum albumin were investigated with proton magnetic resonance (1HMR) spectrometry. The histidinyl side chain of the dipeptide is responsible for primary recognition by the binding site. Furthermore, recognition is specific to a particular orientation of the histidinyl side chain that is determined by the other amino acid residue of the dipeptide. It was found that, although salts do not have a great effect on the binding of carnosine to bovine serum albumin, this binding cannot be measured by equilibrium dialysis in the presence of salt because of formation of a complex Donnan equilibrium. Carnosine, which has been postulated to have a role in olfaction, binds to the crude particulate fraction of nasal olfactory epithelium in the same steric orientation as it does to bovine serum albumin. Therefore, we have used the binding of carnosine to bovine serum albumin as a model system to test potential competitive inhibitors of carnosine binding that ultimately could be tested for activity in the olfactory pathway. It was found that the binding of carnosine to bovine serum albumin is a good model of nonspecific binding of carnosine to tissue preparations but not of the specific binding of carnosine to the nasal olfactory epithelium. In addition to requiring the proper conformation of the histidinyl residue, the binding to olfactory epithelium also appears to require recognition of the β-alanyl residue and of substituents on the imidazole ring. Evidence is provided that the carnosine binding by the nasal olfactory epithelium demonstrated by 1HMR spectroscopy does not occur with the mature olfactory receptor neurons. © 1979.
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页码:529 / 542
页数:14
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