Department of Drug Design and Pharmacology, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark.
Medicinal Chemistry Research Group, Research Center for Natural Sciences, Budapest H-1117, Hungary.
Nucleic Acids Res. 2021 Jan 8;49(D1):D335-D343. doi: 10.1093/nar/gkaa1080.
G protein-coupled receptors (GPCRs) form both the largest family of membrane proteins and drug targets, mediating the action of one-third of medicines. The GPCR database, GPCRdb serves >4 000 researchers every month and offers reference data, analysis of own or literature data, experiment design and dissemination of published datasets. Here, we describe new and updated GPCRdb resources with a particular focus on integration of sequence, structure and function. GPCRdb contains all human non-olfactory GPCRs (and >27 000 orthologs), G-proteins and arrestins. It includes over 2 000 drug and in-trial agents and nearly 200 000 ligands with activity and availability data. GPCRdb annotates all published GPCR structures (updated monthly), which are also offered in a refined version (with re-modeled missing/distorted regions and reverted mutations) and provides structure models of all human non-olfactory receptors in inactive, intermediate and active states. Mutagenesis data in the GPCRdb spans natural genetic variants, GPCR-G protein interfaces, ligand sites and thermostabilising mutations. A new sequence signature tool for identification of functional residue determinants has been added and two data driven tools to design ligand site mutations and constructs for structure determination have been updated extending their coverage of receptors and modifications. The GPCRdb is available at https://gpcrdb.org.
G 蛋白偶联受体 (GPCR) 是膜蛋白家族中最大的家族之一，也是药物靶点，介导三分之一的药物的作用。GPCR 数据库 GPCRdb 每月为 >4000 名研究人员提供服务，提供参考数据、自身或文献数据的分析、实验设计以及已发表数据集的传播。在这里，我们将描述新的和更新的 GPCRdb 资源，特别关注序列、结构和功能的整合。GPCRdb 包含所有人类非嗅觉 GPCR（和 >27000 个直系同源物）、G 蛋白和 arrestins。它包含超过 2000 种药物和临床试验药物以及近 200000 种具有活性和可用性数据的配体。GPCRdb 注释了所有已发表的 GPCR 结构（每月更新），还提供了经过改进的版本（对缺失/扭曲区域进行了重新建模，并对突变进行了反转），并提供了所有人类非嗅觉受体在非活性、中间和活性状态下的结构模型。GPCRdb 中的诱变数据涵盖了天然遗传变异、GPCR-G 蛋白界面、配体结合位点和热稳定突变。新增了一种用于识别功能残基决定因素的序列特征工具，并且两种基于数据的工具也进行了更新，用于设计配体结合位点突变和结构测定构建体，从而扩大了它们对受体和修饰的覆盖范围。GPCRdb 可在 https://gpcrdb.org 上获得。
