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The adenosine A1 receptor (A1-AR) is a G-protein-coupled receptor that plays a vital role in cardiac, renal, and neuronal processes but remains poorly targeted by current drugs. We determined a 3.2 Å crystal structure of the A1-AR bound to the selective covalent antagonist, DU172, and identified striking differences to the previously solved adenosine A2A receptor (A2A-AR) structure. Mutational and computational analysis of A1-AR revealed a distinct conformation of the second extracellular loop and a wider extracellular cavity with a secondary binding pocket that can accommodate orthosteric and allosteric ligands. We propose that conformational differences in these regions, rather than amino-acid divergence, underlie drug selectivity between these adenosine receptor subtypes. Our findings provide a molecular basis for AR subtype selectivity with implications for understanding the mechanisms governing allosteric modulation of these receptors, allowing the design of more selective agents for the treatment of ischemia-reperfusion injury, renal pathologies, and neuropathic pain.
Pubmed ID: 28235198 RIS Download
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A molecular visualization program for displaying, animating, and analyzing large biomolecular systems using 3-D graphics and built-in scripting. VMD supports computers running MacOS X, Unix, or Windows, is distributed free of charge, and includes source code.
View all literature mentionsSoftware for x-ray detection and processing single-crystal monochromatic diffraction data recorded by the rotation method. XDS can process data images from CCD-, imaging-plate-, multiwire-, and pixel-detectors in a variety of formats.
View all literature mentionsData processing software for x-ray diffraction data. AIMLESS scales together multiple observations of reflections, and merges multiple observations into an average intensity.
View all literature mentionsTHIS RESOURCE IS NO LONGER IN SERVICE, documented on July 15, 2013. Database covering a range of plant pathogenic oomycetes, fungi and bacteria primarily those under study at Virginia Bioinformatics Institute. The data comes from different sources and has genomes of 3 oomycetes pathogens: Phytophthora sojae, Phytophthora ramorum and Hyaloperonospora arabidopsidis. The genome sequences (95 MB for P.sojae and 65 MB for P.ramorum) were annotated with approximately 19,000 and approximately 16,000 gene models, respectively. Two different statistical methods were used to validate these gene models, Fickett''''s and a log-likelihood method. Functional annotation of the gene models is based on results from BlastX and InterProScan screens. From the InterProScan results, putative functions to 17,694 genes in P.sojae and 14,700 genes in P.ramorum could be assigned. An easy-to-use genome browser was created to view the genome sequence data, which opens to detailed annotation pages for each gene model. A community annotation interface is available for registered community members to add or edit annotations. There are approximately 1600 gene models for P.sojae and approximately 700 models for P.ramorum that have already been manually curated. A toolkit is provided as an additional resource for users to perform a variety of sequence analysis jobs.
View all literature mentionsParallel molecular dynamics code designed for high-performance simulation of large biomolecular systems. NAMD uses the popular molecular graphics program VMD for simulation setup and trajectory analysis, but is also file-compatible with AMBER, CHARMM, and X-PLOR.
View all literature mentionsMolecular graphics environment which provides biologists and chemists with representations of proteins, DNA, RNA, and multiple sequence alignments. Users can build, annotate, and edit interactive views and slides of molecules. Users can also superimpose protein structures, search PDB, measure distanaces and angles, and view and make high resolution images of alignments.
View all literature mentionsStatistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.
View all literature mentionsA user-sponsored molecular visualization software system on an open-source foundation. The software has the capabilities to view, render, animate, export, present and develop three dimensional molecular structures.
View all literature mentionsA structure-validation web application which provides an expert-system consultation about the accuracy of a macromolecular structure model, diagnosing local problems and enabling their correction. MolProbity works best as an active validation tool (used as soon as a model is available and during each rebuild/refine loop) and when used for protein and RNA crystal structures, but it may also work well for DNA, ligands and NMR ensembles. It produces coordinates, graphics, and numerical evaluations that integrate with either manual or automated use in systems such as PHENIX, KiNG, or Coot.
View all literature mentionsSoftware for macromolecular model building, model completion and validation, and protein modelling using X-ray data. Coot displays maps and models and allows model manipulations such as idealization, rigid-body fitting, ligand search, Ramachandran plots, non-crystallographic symmetry and more. Source code is available.
View all literature mentionsDatabase of annotated three-dimensional comparative protein structure models generated by the fully automated homology-modelling pipeline SWISS-MODEL.
View all literature mentionsCrystallographic software which solves structures using algorithms and automated rapid search calculations to perform molecular replacement and experimental phasing methods.
View all literature mentionsCell line 4E11 [Mouse hybridoma against FLAG peptide] is a Hybridoma with a species of origin Mus musculus (Mouse)
View all literature mentionsThe SciCrunch Infrastructure was developed as a cooperative data platform to be used by diverse communities in making data more FAIR.
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