ISPyB for BioSAXS, the gateway to user autonomy in solution scattering experiments.

Logging experiments with the laboratory-information management system ISPyB (Information System for Protein crystallography Beamlines) enhances the automation of small-angle X-ray scattering of biological macromolecules in solution (BioSAXS) experiments. The ISPyB interface provides immediate user-oriented online feedback and enables data cross-checking and downstream analysis. To optimize data quality and completeness, ISPyBB (ISPyB for BioSAXS) makes it simple for users to compare the results from new measurements with previous acquisitions from the same day or earlier experiments in order to maximize the ability to collect all data required in a single synchrotron visit. The graphical user interface (GUI) of ISPyBB has been designed to guide users in the preparation of an experiment. The input of sample information and the ability to outline the experimental aims in advance provides feedback on the number of measurements required, calculation of expected sample volumes and time needed to collect the data: all of this information aids the users to better prepare for their trip to the synchrotron. A prototype version of the ISPyBB database is now available at the European Synchrotron Radiation Facility (ESRF) beamline BM29 and is already greatly appreciated by academic users and industrial clients. It will soon be available at the PETRA III beamline P12 and the Diamond Light Source beamlines I22 and B21.

Upgraded ESRF BM29 beamline for SAXS on macromolecules in solution.

Small-angle X-ray scattering (SAXS) measurements of proteins in solution are becoming increasingly popular with biochemists and structural biologists owing to the presence of dedicated high-throughput beamlines at synchrotron sources. As part of the ESRF Upgrade program a dedicated instrument for performing SAXS from biological macromolecules in solution (BioSAXS) has been installed at the renovated BM29 location. The optics hutch has been equipped with new optical components of which the two principal elements are a fixed-exit double multilayer monochromator and a 1.1 m-long toroidal mirror. These new dedicated optics give improved beam characteristics (compared with the previous set-up on ID14-3) regarding the energy tunability, flux and focusing at the detector plane leading to reduced parasitic scattering and an extended s-range. User experiments on the beamline have been successfully carried out since June 2012. A description of the new BioSAXS beamline and the set-up characteristics are presented together with examples of obtained data.

Increased omeprazole metabolism in carriers of the CYP2C19*17 allele; a pharmacokinetic study in healthy volunteers.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: The only existing study of CYP2C19*17-associated alterations in drug pharmacokinetics was retrospective and compared probe drug metabolic ratios. The CYP2C19*17 allele had been associated with a two- and fourfold decrease in omeprazole and S/R-mephenytoin metabolic ratios. WHAT THIS STUDY ADDS: This study characterized the single-dose pharmacokinetics of omeprazole, along with the 5-hydroxy and sulphone metabolites, in CYP2C19*17/*17 and CYP2C19*1/*1 subjects. The observed differences in omeprazole AUC(infinity) suggest that the CYP2C19*17 allele is an important explanatory factor behind individual cases of therapeutic failure. AIMS To investigate the influence of the CYP2C19*17 allele on the pharmacokinetics of omeprazole, a commonly used CYP2C19 probe drug, in healthy volunteers. METHODS: In a single-dose pharmacokinetic study, 17 healthy White volunteers genotyped as either CYP2C19*17/*17 or CYP2C19*1/*1 received an oral dose of 40 mg of omeprazole. Plasma was sampled for up to 10 h postdose, followed by quantification of omeprazole, 5-hydroxy omeprazole and omeprazole sulphone by high-performance liquid chromatography. RESULTS: The mean omeprazole AUC(infinity) of 1973 h nmol l(-1) in CYP2C19*17/*17 subjects was 2.1-fold lower [95% confidence interval (CI) 1.1, 3.3] than in CYP2C19*1/*1 subjects (4151 h nmol l(-1), P = 0.04). A similar trend was observed for the sulphone metabolite with the CYP2C19*17/*17 group having a mean AUC(infinity) of 1083 h nmol l(-1), 3.1-fold lower (95% CI 1.2, 5.5) than the CYP2C19*1/*1 group (3343 h nmol l(-1), P = 0.03). A pronounced correlation (r(2) = 0.95, P < 0.0001) was seen in the intraindividual omeprazole AUC(infinity) and omeprazole sulphone AUC(infinity) values. CONCLUSIONS: The pharmacokinetics of omeprazole and omeprazole sulphone differ significantly between homozygous CYP2C19*17 and CYP2C19*1 subjects. For clinically important drugs that are metabolized predominantly by CYP2C19, the CYP2C19*17 allele might be associated with subtherapeutic drug exposure.