G protein-coupled receptors database

The GPCRdb database is the main repository of curated data for G protein-coupled receptors (GPCRs). It integrates various web tools and diagrams for GPCR analysis and stores manual annotations of all GPCR crystal structures made available through the PDB (Protein Data Bank), has the largest collections of receptor mutants and reference sequence alignments. A series of tools made available in the homepage for the GPCRdb can be run in the web browser to analyze structures, sequence similarities, receptor relationships, homology models, drug trends, genetic variants and ligand target profiles. Diagrams illustrate receptor sequences (using snake-plots and helix box diagrams) and relationships (phylogenetic trees).

GPCRDB
Content
DescriptionG protein-coupled receptor data, web tools & diagrams
Data types
captured		Structures, mutants, sequences
Contact
Research centerUniversity of Copenhagen
AuthorsVignir Isberg, Bas Vrolin, Gert Vriend, David Gloriam and others.
Primary citationPandy-Szekeres G, Munk C, Tsonkov TM, Mordalski S, Harpsoe K, Hauser AS, Bojarski AJ, Gloriam DE. [1]
Release date1993
Access
Websitehttps://www.gpcrdb.org
Web service URLhttps://gpcrdb.org/services/
Miscellaneous
Curation policyManual and experimental data-derived

Background and development

According to Gert Vriend, one of the starters of the GPCRdb, the resource began in the following way:

"The GPCRdb was started in the early 90’s when Bob Bywater, Ad IJzerman, Friedrich Rippmann, and Gert Vriend organized a series of small GPCR workshops at the EMBL. Before the introduction of the first browsers, the GPCRdb worked as an automatic Email answering system that could send sequences, alignments, and homology models to the users. In 1994 the internet was firmly established in its present form, and money was obtained from the fourth EU framework to set up the GPCRdb. Florence Horn joined us to do this project. When she left us at the end of a four-year post-doc period the GPCRdb was firmly established as the prime source of information for GPCR data." [2]

Over two decades, the GPCRdb evolved to be a comprehensive information system storing and analyzing data. In 2013, the stewardship of the GPCRdb was transferred to David Gloriam's group at the University of Copenhagen, backed up by an international team of contributors and developers from a EU COST Action called ‘GLISTEN’. Today, the GPCRdb offers reference data and easy-to-use web tools and diagrams for a multidisciplinary audience investigating GPCR function, drug design or evolution.

Content and features

A visual overview of the main features of the GPCRdb can be glimpsed at gpcrdb.org.

The GPCRdb browsing system is structured on the most relevant categories for the GPCR community:

  • GPCRdb[3]
  • Receptors[4]
  • G Proteins[5]
  • B-Arrestins
  • Biased Signaling
  • Ligands[6]
  • Drugs[7]
  • Structure Constructs
  • Tutorial

Under the categories one can find subsections for specialized data and tools.

Future directions

As part of two orphan GPCR projects funded by the European Research Commission and the Lundbeck Foundation, respectively, the GPCRdb will deposit data and develop computational tools for identification of endogenous and surrogate GPCR ligands. The GPCRdb aims to grow from and enable new progress in GPCR structure, function and ligand design. It crosslinks to the GuideToPharmacology database and has adopted the official NC-IUPHAR receptor naming nomenclature, has exchange with GPCR servers, and has also recently become part of the GPCR Consortium set out to generate an unprecedented number of crystal structures. Academic and industrial groups are welcome and encouraged to contact the GPCRdb with suggestions for joint development or data deposition.

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See also

References
  1. Pandy-Szekeres, Gaspar; Munk, Christian; Tsonkov, Tsonko; Mordalski, Stefan; Harpsoe, Kasper; Hauser, Alexander; Bojarski, Andrzej; Gloriam, David (2017-11-16). "GPCRdb in 2018: adding GPCR structure models and ligands". Nucleic Acids Research. 46 (D1): D440–D446. doi:10.1093/nar/gkx1109.
  2. "Acknowledgements — GPCRdb 3 documentation". docs.gpcrdb.org. Retrieved 2020-08-05.
  3. Isberg, Vignir; Graaf, Chris de; Bortolato, Andrea; Cherezov, Vadim; Katritch, Vsevolod; Marshall, Fiona H.; Mordalski, Stefan; Pin, Jean-Philippe; Stevens, Raymond C. (2015-01-01). "Generic GPCR residue numbers – aligning topology maps while minding the gaps". Trends in Pharmacological Sciences. 36 (1): 22–31. doi:10.1016/j.tips.2014.11.001. PMC 4408928. PMID 25541108.
  4. Hauser, Alexander S.; Chavali, Sreenivas; Masuho, Ikuo; Jahn, Leonie J.; Martemyanov, Kirill A.; Gloriam, David E.; Babu, M. Madan (2018). "Pharmacogenomics of GPCR Drug Targets". Cell. 172 (1–2): 41–54.e19. doi:10.1016/j.cell.2017.11.033. PMC 5766829. PMID 29249361.
  5. Flock, Tilman; Hauser, Alexander S.; Lund, Nadia; Gloriam, David E.; Balaji, Santhanam; Babu, M. Madan (May 2017). "Selectivity determinants of GPCR–G-protein binding". Nature. 545 (7654): 317–322. doi:10.1038/nature22070. ISSN 1476-4687. PMC 5846738. PMID 28489817.
  6. Pándy-Szekeres, Gáspár; Munk, Christian; Tsonkov, Tsonko M.; Mordalski, Stefan; Harpsøe, Kasper; Hauser, Alexander S.; Bojarski, Andrzej J.; Gloriam, David E. (2018). "GPCRdb in 2018: adding GPCR structure models and ligands". Nucleic Acids Research. 46: D440–D446. doi:10.1093/nar/gkx1109. PMC 5753179. PMID 29155946.
  7. Hauser, Alexander S.; Attwood, Misty M.; Rask-Andersen, Mathias; Schiöth, Helgi B.; Gloriam, David E. (December 2017). "Trends in GPCR drug discovery: new agents, targets and indications". Nature Reviews Drug Discovery. 16 (12): 829–842. doi:10.1038/nrd.2017.178. ISSN 1474-1784. PMC 6882681. PMID 29075003.
  • GPCRdb GPCR database
  • GLISTEN EU COST Action for GPCRs
  • GPCR-HGmod Predicted structure models of all GPCRs in human genome
  • GPCR-EXP Database for all experimentally solved GPCR structures


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