期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 275, 期 48, 页码 37779-37788出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M002092200
关键词
-
资金
- NIMH NIH HHS [MH54137, MH57324] Funding Source: Medline
Previous work in the beta (2)-adrenergic receptor demonstrated critical interactions between Ser-204 and Ser-207 in the fifth membrane-spanning segment and the meta-OH and para-Os, respectively, of catecholamine agonists (Strader, C. D., Candelore, M, R., Hill, W. S., Sigal, I. S., and Dixon, R, A. (1989) J. Biol. Chem. 264, 13572-13578). Using the substituted cysteine accessibility method in the beta (2)-adrenergic receptor, we have found that in addition to Ser-204 and Ser-207, Ser-203 is also accessible on the surface of the binding-site crevice and is occluded by bound agonist. Mutation of Ser-203 to Ala, Val, or Cys reduced the binding affinity and adenylyl cyclase-activating potency of agonists containing a meta-OH, whereas their affinities and potencies were largely preserved by mutation of Ser-203 to Thr, which maintained an OH at this position. Thus both Ser-203 and Ser-204 appear to interact with the meta-OH of catecholamines, perhaps through a bifurcated H bond. Furthermore, the removal of the OH at position 203 led to a significant loss of affinity of antagonists with nitrogen in their heterocyclic ring structure. The greatest effect was seen with pindolol, a partial agonist, suggesting that a H bond between the heterocyclic ring and Ser-203 may play a role in partial agonism. In contrast, the affinities of antagonists such as propranolol or alprenolol, which have cyclic structures without H-bonding capability, were unaltered after mutation of Ser-203.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据