Automated assignment of ambiguous nuclear overhauser effects with ARIA.
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Magnetic Resonance Spectroscopy↗
Biomedical subjects
J P Linge
Publications and source records attributed to J P Linge.
Refinement of the protein backbone angle psi in NMR structure calculations.
Cross-correlated relaxation rates involving the Calpha-Halpha dipolar interaction and the carbonyl (C') chemical shift anisotropy (CSA) have been measured using two complementary 3D experiments. We show that the protein backbone angle psi can be directly refined against such cross-correlated relaxation rates (gammaHalphaCalpha,C') and the three-bond H/D isotope effect on the Calpha chemical shifts (3 deltaCalpha(ND)). By simultaneously using both experimental parameters as restraints during NMR structure calculations, a unique value for the backbone angle psi is defined. We have applied the new refinement method to the alpha-Spectrin SH3 domain (a beta-sheet protein) and to the Sgs1p HRDC domain (an alpha-helical protein) and show that the quality of the NMR structures is substantially improved, judging from the atomic coordinate precision and the Ramachandran map. In addition, the psi-refined NMR structures of the SH3 domain deviate less from the 1.8 A crystal structure, suggesting an improved accuracy. The proposed refinement method can be used to significantly improve the quality of NMR structures and will be applicable to larger proteins.
Carbon↗
The three-dimensional structure of the HRDC domain and implications for the Werner and Bloom syndrome proteins.
BACKGROUND: The HRDC (helicase and RNaseD C-terminal) domain is found at the C terminus of many RecQ helicases, including the human Werner and Bloom syndrome proteins. RecQ helicases have been shown to unwind DNA in an ATP-dependent manner. However, the specific functional roles of these proteins in DNA recombination and replication are not known. An HRDC domain exists in both of the human RecQ homologues that are implicated in human disease and may have an important role in their function. RESULTS: We have determined the three-dimensional structure of the HRDC domain in the Saccharomyces cerevisiae RecQ helicase Sgs1p by nuclear magnetic resonance (NMR) spectroscopy. The structure resembles auxiliary domains in bacterial DNA helicases and other proteins that interact with nucleic acids. We show that a positively charged region on the surface of the Sgs1p HRDC domain can interact with DNA. Structural similarities to bacterial DNA helicases suggest that the HRDC domain functions as an auxiliary domain in RecQ helicases. Homology models of the Werner and Bloom HRDC domains show different surface properties when compared with Sgs1p. CONCLUSIONS: The HRDC domain represents a structural scaffold that resembles auxiliary domains in proteins that are involved in nucleic acid metabolism. In Sgs1p, the HRDC domain could modulate the helicase function via auxiliary contacts to DNA. However, in the Werner and Bloom syndrome helicases the HRDC domain may have a role in their functional differences by mediating diverse molecular interactions.
Adenosine Triphosphatases↗
StarDOM: from STAR format to XML.
StarDOM is a software package for the representation of STAR files as document object models and the conversion of STAR files into XML. This allows interactive navigation by using the Document Object Model representation of the data as well as easy access by XML query languages. As an example application, the entire BioMagResBank has been transformed into XML format. Using an XML query language, statistical queries on the collected NMR data sets can be constructed with very little effort. The BioMagResBank/XML data and the software can be obtained at http://www.nmr.embl-heidelberg.de/nmr/StarDOM linge@embl-heidelberg.de
Databases, Factual↗
Influence of non-bonded parameters on the quality of NMR structures: a new force field for NMR structure calculation.
The effects of different non-bonded parameters of force fields for NMR structure calculation on the quality of the resulting NMR solution structures were investigated using Interleukin 4 as a model system. NMR structure ensembles were calculated with an ab initio protocol using torsion angle dynamics. The calculations were repeated with five different non-bonded energy functions and parameters. The resulting ensembles were compared with the available X-ray structures, and their quality was assessed with common structure validation programs. In addition, the impact of torsion angle restraints and dihedral energy terms for the sidechains and the backbone was studied. The further improvement of the quality by refinement in explicit solvent was demonstrated. The optimal parameters, including those necessary for water refinement, are available in the new version of the PARALLHDG force field.
Interleukin-4↗