Structures of 70 unique G protein-coupled receptors (GPCRs) have been determined, with over 370 structures in total bound to different ligands and the receptors in various conformational states. Structure-based drug design has been applied to an increasing number of GPCR targets over the past ...
Structures of GPCRs 冷冻电镜解GPCR结构的分辨率,大多在3.0-3.5A,在正构结合口袋周围会更差。 The Current State of Drug Discovery for GPCRs 目前的药物治疗靶点只靶向25%的可成药GPCR,共103个(可成药靶点共403个)。其中41个是激动剂,27个是拮抗剂,35个既有激动剂又有拮抗剂。 近年来,一些以往被非选择性...
IBC's Drug Discovery Technology Series is a group of conferences highlighting technological advances and applications in niche areas of the drug discovery pipeline. This 2-day meeting focused on G-protein-coupled receptors (GPCRs), probably the most important and certainly the most valuable class of...
While G-protein coupled receptors (GPCRs) represent a highly druggable target (20 % of all drugs approved since 1983), the ‘golden age of GPCR structural biology’ starting in the early 2000s further drove the elucidation of their three-dimensional (3D) structures [8]. Consequently, specific...
Recent breakthroughs in the determination of the crystal structures of G protein-coupled receptors (GPCRs) have provided new opportunities for structure-ba... M Michino,E Abola,CL Brooks,... - 《Nature Reviews Drug Discovery》 被引量: 377发表: 2009年 Evaluation of DOCK 6 as a pose generatio...
While high resolution structures of all class B GPCRs have now been solved, typically using cryo-electron microscopy (cryo-EM)10,11,12,13,14,15,16,17, all of these have been monomeric forms of the receptor. Homo-dimerization of the SecR has been demonstrated by saturation bioluminescence res...
Comparative modeling relies on the fact that structure is more conserved than sequence during evolution. Therefore, similar sequences exhibit nearly identical structures, and even distantly related sequences share the same fold [7, 8]. Comparative modeling critically depends on the knowledge of three-...
For instance, citric and TCA cycle, ATP synthesis, and translation (at the margin and inside of the HCC and MASH-HCC tumors) were upregulated in HCC but downregulated in MASH-HCC. Interestingly, GPCR (G protein-coupled receptor) ligand binding was inhibited in MASH-HCC but upregulated in ...
structures22, the extent to which these isoforms influence gene expression levels, impact phenotypes and/or are important for organismal fitness is unknown. Assessing these questions is complicated partly because the rapid decay of unproductive isoforms obscures quantitative measurements of their splicing7...
and structure determination by X-ray crystallography and NMR. These efforts resulted in the determination of over 13,500 protein structures, mostly from unique protein families, and increased the structural coverage of the expanding protein universe. SG programs contributed over 4400 publications to the...