A Structure-Based Approach to Understanding Somatostatin Receptor-4 Agonism (sst4)

被引：18
|
作者：
Liu, Zhaomin [1 ]
Crider, A. Michael [1 ,2 ]
Ansbro, Daniel [2 ]
Hayes, Christina [2 ]
Kontoyianni, Maria [1 ,2 ]
机构：
[1] So Illinois Univ, Dept Chem, Edwardsville, IL 62026 USA
[2] So Illinois Univ, Dept Pharmaceut Sci, Edwardsville, IL 62026 USA
来源：
JOURNAL OF CHEMICAL INFORMATION AND MODELING | 2012年 / 52卷 / 01期
关键词：
PROTEIN-COUPLED RECEPTORS; BETA(2) ADRENERGIC-RECEPTOR; A(2A) ADENOSINE RECEPTOR; CONSERVED ASPARTIC-ACID; CRYSTAL-STRUCTURE; TRANSMEMBRANE DOMAIN; BINDING AFFINITIES; DRUGGABLE GENOME; ACCURATE DOCKING; FLEXIBLE DOCKING;
D O I：
10.1021/ci200375j
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
It has been reported that somatostatin receptor subtypes 4 and 5 would be high-impact templates for homology modeling if their 3D structures became available. We have generated a homology model of the somatostatin receptor subtype 4 (sst4), using the newest active state beta(2) adrenoreceptor crystal structure, and subsequently docked a variety of agonists into the model-built receptor to elucidate the binding modes of reported agonists. Using experimental restraints, we were able to explain observed activity profiles. We propose two binding modes that can consistently explain findings for high-affinity agonists and reason why certain structures display low affinities for the receptor.
引用
收藏
页码：171 / 186
页数：16
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