Exploiting X-ray induced anisotropic lattice changes to improve intensity extraction in protein powder diffraction: Application to heavy atom detection

Besnard, Céline; Camus, Fabrice; Fleurant, M.; Dahlström, Alexander; Wright, J.P.; Margiolaki, I.; Pattison, Philippa; Schiltz, M.

doi:10.1524/zksu.2007.2007.suppl_26.39

Cited by 9 publications

(9 citation statements)

References 6 publications

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“…One common phenomenon is an irreversible radiation-induced lattice expansion, although the mechanism by which this occurs is not fully understood (Ravelli et al, 2002). In many cases, lattice changes are anisotropic and can thus be exploited to improve the resolution of overlapping reflections in a powder pattern (Basso et al, 2005;Von Dreele, 2007;Besnard et al, 2007;Margiolaki, Wright, Wilmanns et al, 2007;Wright et al, 2008;Basso et al, 2010;Helliwell et al, 2010). In the case of powder diffraction data, significant changes in the lattice parameters accompanied by a gradual increase of peak broadening and a significant loss of intensity are common characteristics of radiation-damage effects (Margiolaki, Wright, Wilmanns et al, 2007).…”

Section: Radiation-and Ph-induced Anisotropic Lattice Modificationsmentioning

confidence: 99%

High-resolution powder X-ray data reveal the T₆hexameric form of bovine insulin

Margiolaki

Giannopoulou

Wright

et al. 2013

Acta Crystallogr D Biol Crystallogr

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A series of bovine insulin samples were obtained as 14 polycrystalline precipitates at room temperature in the pH range 5.0-7.6. High-resolution powder X-ray diffraction data were collected to reveal the T6 hexameric insulin form. Sample homogeneity and reproducibility were verified by additional synchrotron measurements using an area detector. Pawley analyses of the powder patterns displayed pH- and radiation-induced anisotropic lattice modifications. The pronounced anisotropic lattice variations observed for T6 insulin were exploited in a 14-data-set Rietveld refinement to obtain an average crystal structure over the pH range investigated. Only the protein atoms of the known structure with PDB code 2a3g were employed in our starting model. A novel approach for refining protein structures using powder diffraction data is presented. In this approach, each amino acid is represented by a flexible rigid body (FRB). The FRB model requires a significantly smaller number of refinable parameters and restraints than a fully free-atom refinement. A total of 1542 stereochemical restraints were imposed in order to refine the positions of 800 protein atoms, two Zn atoms and 44 water molecules in the asymmetric unit using experimental data in the resolution range 18.2-2.7 Å for all profiles.

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Section: Radiation-and Ph-induced Anisotropic Lattice Modificationsmentioning

confidence: 99%

High-resolution powder X-ray data reveal the T₆hexameric form of bovine insulin

Margiolaki

Giannopoulou

Wright

et al. 2013

Acta Crystallogr D Biol Crystallogr

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“…One of the major bottlenecks in macromolecular XRPD has always been the loss of structural information owing to the severe overlap of powder diffraction peaks (Rietveld, 1969;Pawley, 1981;David, 1987David, , 1999Besnard et al, 2007;Toby & Von Dreele, 2013;Dinnebier et al, 2019;Margiolaki, 2019;Von Dreele, 2019;. Thus, data collection strategies are continuously improved towards amelioration of the obtainable resolution (angular and d-spacing), enabling, therefore, the discrimination between adjacent Bragg peaks.…”

Section: Discussionmentioning

confidence: 99%

New perspectives in macromolecular powder diffraction using single-photon-counting strip detectors: high-resolution structure of the pharmaceutical peptide octreotide

Spiliopoulou

Karavassili

Triandafillidis

et al. 2021

Acta Crystallogr A Found Adv

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Advances in instrumentation, as well as the development of powerful crystallographic software have significantly facilitated the collection of high-resolution diffraction data and have made X-ray powder diffraction (XRPD) particularly useful for the extraction of structural information; this is true even for complex molecules, especially when combined with synchrotron radiation. In this study, in-line with past instrumental profile studies, an improved data collection strategy exploiting the MYTHEN II detector system together with significant beam focusing and tailored data collection options was introduced and optimized for protein samples at the Material Science beamline at the Swiss Light Source. Polycrystalline precipitates of octreotide, a somatostatin analog of particular pharmaceutical interest, were examined with this novel approach. XRPD experiments resulted in high angular and d-spacing (1.87 Å) resolution data, from which electron-density maps of enhanced quality were extracted, revealing the molecule's structural properties. Since microcrystalline precipitates represent a viable alternative for administration of therapeutic macromolecules, XRPD has been acknowledged as the most applicable tool for examining a wide spectrum of physicochemical properties of such materials and performing studies ranging from phase identification to complete structural characterization.

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“…As radiation damage is a major concern in macromolecular X-ray diffraction measurements (Besnard et al, 2007;Garman, 2010;Sliz et al, 2003;Watier, 2011), data collection was performed using a combination of data collected employing a laboratory instrument, an ultra-high-resolution synchrotron beamline with a multi-crystal analyser detector stage and a high-resolution/high-throughput synchrotron beamline with a single-photon-counting detector. Exploratory measurements were carried out on an in-house diffractometer (X'Pert Pro, Malvern Panalytical) using Debye-Scherrer geometry with Cu K 1 radiation [ = 1.540585 (3) Å ] (Hö lzer et al, 1997) at room temperature, which allowed us to precharacterize all samples.…”

Section: Xrpd Data Collection and Processingmentioning

confidence: 99%

High-throughput macromolecular polymorph screening via an NMR and X-ray powder diffraction synergistic approach: the case of human insulin co-crystallized with resorcinol derivatives

et al. 2021

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Regular injections of insulin provide life-saving benefits to millions of diabetics. Apart from native insulin and insulin analogue formulations, microcrystalline insulin suspensions are also commercially available. The onset of action of the currently available basal insulins relies on the slow dissociation of insulin hexamers in the subcutaneous space due to the strong binding of small organic ligands. With the aim of identifying insulin–ligand complexes with enhanced pharmacokinetic and pharmacodynamic profiles, the binding affinity of two resorcinol-based molecules (4-chlororesorcinol and 4-bromoresorcinol) and the structural characteristics of insulin upon co-crystallization with them were investigated in the present study. `In solution' measurements were performed via saturation transfer difference (STD) NMR. Co-crystallization upon pH variation resulted in the production of polycrystalline precipitates, whose structural characteristics (i.e. unit-cell symmetry and dimension) were assessed. In both cases, different polymorphs (four and three, respectively) of monoclinic symmetry (P21 and C2 space groups) were identified via X-ray powder diffraction. The results demonstrate the efficiency of a new approach that combines spectroscopy and diffraction techniques and provides an innovative alternative for high-throughput examination of insulin and other therapeutic proteins.

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Exploiting X-ray induced anisotropic lattice changes to improve intensity extraction in protein powder diffraction: Application to heavy atom detection

Cited by 9 publications

References 6 publications

High-resolution powder X-ray data reveal the T₆hexameric form of bovine insulin

High-resolution powder X-ray data reveal the T₆hexameric form of bovine insulin

New perspectives in macromolecular powder diffraction using single-photon-counting strip detectors: high-resolution structure of the pharmaceutical peptide octreotide

High-throughput macromolecular polymorph screening via an NMR and X-ray powder diffraction synergistic approach: the case of human insulin co-crystallized with resorcinol derivatives

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Exploiting X-ray induced anisotropic lattice changes to improve intensity extraction in protein powder diffraction: Application to heavy atom detection

Cited by 9 publications

References 6 publications

High-resolution powder X-ray data reveal the T6hexameric form of bovine insulin

High-resolution powder X-ray data reveal the T6hexameric form of bovine insulin

New perspectives in macromolecular powder diffraction using single-photon-counting strip detectors: high-resolution structure of the pharmaceutical peptide octreotide

High-throughput macromolecular polymorph screening via an NMR and X-ray powder diffraction synergistic approach: the case of human insulin co-crystallized with resorcinol derivatives

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Product

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High-resolution powder X-ray data reveal the T₆hexameric form of bovine insulin

High-resolution powder X-ray data reveal the T₆hexameric form of bovine insulin