GPCRDB information system for G protein-coupled receptors.

Contains fulltext : 185042.pdf (publisher's version ) (Open Access)The GPCRDB is a molecular class-specific information system that collects, combines, validates and disseminates heterogeneous data on G protein-coupled receptors (GPCRs). The database stores data on sequences, ligand binding constants and mutations. The system also provides computationally derived data such as sequence alignments, homology models, and a series of query and visualization tools. The GPCRDB is updated automatically once every 4-5 months and is freely accessible at http://www.gpcr.org/7tm/

Batch mode generation of residue-based diagrams of proteins.

Item does not contain fulltextSUMMARY: Residue-based diagrams of proteins are graphical representations that can be used in protein information systems. These diagrams make it possible to visually integrate different types of biological information. The approach has been used successfully for membrane proteins. We developed the Residue-based diagram generator to (i) make it possible to generate residue-based diagrams of proteins in a batch mode that is compatible with the needs of information system curators, (ii) allow the generation of residue-based diagrams for families of soluble proteins or domains. AVAILABILITY: Licensed. Royalty free licenses are granted to non-profit institutions for educational and research purposes. http://icb.mssm.edu/crt/RbDg/index.xm

The nuclear receptor ligand-binding domain: a family-based structure analysis

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A family-based approach reveals the function of residues in the nuclear receptor ligand-binding domain.

Contains fulltext : 57293.pdf (publisher's version ) (Closed access)Literature studies, 3D structure data, and a series of sequence analysis techniques were combined to reveal important residues in the structure and function of the ligand-binding domain of nuclear hormone receptors. A structure-based multiple sequence alignment allowed for the seamless combination of data from many different studies on different receptors into one single functional model. It was recently shown that a combined analysis of sequence entropy and variability can divide residues in five classes; (1) the main function or active site, (2) support for the main function, (3) signal transduction, (4) modulator or ligand binding and (5) the rest. Mutation data extracted from the literature and intermolecular contacts observed in nuclear receptor structures were analyzed in view of this classification and showed that the main function or active site residues of the nuclear receptor ligand-binding domain are involved in cofactor recruitment. Furthermore, the sequence entropy-variability analysis identified the presence of signal transduction residues that are located between the ligand, cofactor and dimer sites, suggesting communication between these regulatory binding sites. Experimental and computational results agreed well for most residues for which mutation data and intermolecular contact data were available. This allows us to predict the role of the residues for which no functional data is available yet. This study illustrates the power of family-based approaches towards the analysis of protein function, and it points out the problems and possibilities presented by the massive amounts of data that are becoming available in the "omics era". The results shed light on the nuclear receptor family that is involved in processes ranging from cancer to infertility, and that is one of the more important targets in the pharmaceutical industry