Diffraction-geometry refinement in the<i>DIALS</i>framework

Waterman, David; Winter, Graeme; Gildea, Richard J.; Parkhurst, James M.; Brewster, Aaron S.; Sauter, Nicholas K.; Evans, Gwyndaf

doi:10.1107/s2059798316002187

Cited by 171 publications

(156 citation statements)

References 37 publications

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“…Images were collected using a PILATUS3‐6M detector (Dectris, Switzerland). Raw data images were indexed and integrated with DIALS 32, and then scaled using AIMLESS 33 from the CCP4 suite 34. Initial phases were obtained by molecular replacement with PHASER 35 using PDB code 1O8A 19 for cACE and 3NXQ 20 for nACE as the search models.…”

Section: Experimental Methodsmentioning

confidence: 99%

Crystal structures of sampatrilat and sampatrilat‐Asp in complex with human ACE – a molecular basis for domain selectivity

et al. 2018

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Angiotensin‐1‐converting enzyme (ACE) is a zinc metallopeptidase that consists of two homologous catalytic domains (known as nACE and cACE) with different substrate specificities. Based on kinetic studies it was previously reported that sampatrilat, a tight‐binding inhibitor of ACE, K i = 13.8 nm and 171.9 nm for cACE and nACE respectively [Sharma et al., Journal of Chemical Information and Modeling (2016), 56, 2486–2494], was 12.4‐fold more selective for cACE. In addition, samAsp, in which an aspartate group replaces the sampatrilat lysine, was found to be a nonspecific and lower micromolar affinity inhibitor. Here, we report a detailed three‐dimensional structural analysis of sampatrilat and samAsp binding to ACE using high‐resolution crystal structures elucidated by X‐ray crystallography, which provides a molecular basis for differences in inhibitor affinity and selectivity for nACE and cACE. The structures show that the specificity of sampatrilat can be explained by increased hydrophobic interactions and a H‐bond from Glu403 of cACE with the lysine side chain of sampatrilat that are not observed in nACE. In addition, the structures clearly show a significantly greater number of hydrophilic and hydrophobic interactions with sampatrilat compared to samAsp in both cACE and nACE consistent with the difference in affinities. Our findings provide new experimental insights into ligand binding at the active site pockets that are important for the design of highly specific domain selective inhibitors of ACE.DatabaseThe atomic coordinates and structure factors for N‐ and C‐domains of ACE bound to sampatrilat and sampatrilat‐Asp complexes (6F9V, 6F9R, 6F9T and 6F9U respectively) have been deposited in the Protein Data Bank, Research Collaboratory for Structural Bioinformatics, Rutgers University, New Brunswick, NJ (http://www.rcsb.org/).

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Section: Experimental Methodsmentioning

confidence: 99%

Crystal structures of sampatrilat and sampatrilat‐Asp in complex with human ACE – a molecular basis for domain selectivity

et al. 2018

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“…The relationships between different data collections can be used to provide additional information in, for example, joint refinement against multiple data sets whose sets of experimental models intersect. This has been detailed in Waterman et al (2016).…”

Section: Data Structuresmentioning

confidence: 99%

“…the image width is less than the mosaic spread; Pflugrath, 1999). A comprehensive discussion of DIALS refinement is given by Waterman et al (2016).…”

Section: Algorithms: Refinementmentioning

confidence: 99%

DIALS: implementation and evaluation of a new integration package

Winter

Waterman

Parkhurst

et al. 2018

Acta Crystallogr D Struct Biol

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935

797

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The DIALS project is a collaboration between Diamond Light Source, Lawrence Berkeley National Laboratory and CCP4 to develop a new software suite for the analysis of crystallographic X-ray diffraction data, initially encompassing spot finding, indexing, refinement and integration. The design, core algorithms and structure of the software are introduced, alongside results from the analysis of data from biological and chemical crystallography experiments.

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“…The data were initially processed with XDS (36), and the structure was solved by molecular replacement using MoRDa (37), which output two copies each of the A domains from 3ip4 and 3dha in the asymmetric unit. After some rebuilding, the new model was used in Phaser with reprocessed data (using Xia2 and DIALS) (38)(39)(40)(41)(42) and this was followed by manual building (COOT) and refinement with Refmac (43). Two complete chains of AtzE (residues 1-457) were located in the asymmetric unit.…”

Section: Heterologous Protein Expression -The Expression Vectors Werementioning

confidence: 99%

An unexpected vestigial protein complex reveals the evolutionary origins of an s-triazine catabolic enzyme

Esquirol

Peat

Wilding

et al. 2018

Journal of Biological Chemistry

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Diffraction-geometry refinement in theDIALSframework

Cited by 171 publications

References 37 publications

Crystal structures of sampatrilat and sampatrilat‐Asp in complex with human ACE – a molecular basis for domain selectivity

Crystal structures of sampatrilat and sampatrilat‐Asp in complex with human ACE – a molecular basis for domain selectivity

DIALS: implementation and evaluation of a new integration package

An unexpected vestigial protein complex reveals the evolutionary origins of an s-triazine catabolic enzyme

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