Elucidating polymorphs of crystal structures by intensity-based hierarchical clustering analysis of multiple diffraction data sets
In macromolecular structure determination using X-ray diffraction from multiple crystals, the presence of different structures (structural polymorphs) necessitates the classification of the diffraction data for appropriate structural analysis. Hierarchical clustering analysis (HCA) is a promising technique that has so far been used to extract isomorphous data, mainly for single-structure determination. Although in principle the use of HCA can be extended to detect polymorphs, the absence of a reference to define the threshold used to group the isomorphous data sets (the `isomorphic threshold') poses a challenge. Here, unit...
Source: Acta Crystallographica Section D - September 25, 2023 Category: Biochemistry Authors: Matsuura, H. Sakai, N. Toma-Fukai, S. Muraki, N. Hayama, K. Kamikubo, H. Aono, S. Kawano, Y. Yamamoto, M. Hirata, K. Tags: polymorph analysis high-data-rate macromolecular crystallography hierarchical clustering analysis automated structure analysis research papers Source Type: research
Michael James (1940 – 2023)
(Source: Acta Crystallographica Section D)
Source: Acta Crystallographica Section D - September 15, 2023 Category: Biochemistry Authors: Glover, J.N.M. Kay, C.M. Lemieux, J. Read, R.J. Tags: obituaries Michael James Source Type: research
Structural basis for the allosteric pathway of 4-amino-4-deoxychorismate synthase
This study provides insights into the structural factors that are involved in the allosteric regulation of ADCS. (Source: Acta Crystallographica Section D)
Source: Acta Crystallographica Section D - September 15, 2023 Category: Biochemistry Authors: Nakamichi, Y. Kobayashi, J. Toyoda, K. Suda, M. Hiraga, K. Inui, M. Watanabe, M. Tags: chorismate allosteric pathways 4-amino-4-deoxychorismate synthase chorismate-utilizing enzymes Streptomyces venezuelae research papers Source Type: research
X-ray structure of the metastable SEPT14 – SEPT7 coiled coil reveals a hendecad region crucial for heterodimerization
Septins are membrane-associated, GTP-binding proteins that are present in most eukaryotes. They polymerize to play important roles as scaffolds and/or diffusion barriers as part of the cytoskeleton. α -Helical coiled-coil domains are believed to contribute to septin assembly, and those observed in both human SEPT6 and SEPT8 form antiparallel homodimers. These are not compatible with their parallel heterodimeric organization expected from the current model for protofilament assembly, but they could explain the interfilament cross-bridges observed by microscopy. Here, the first structure of a heterodimeric septin coiled coi...
Source: Acta Crystallographica Section D - September 15, 2023 Category: Biochemistry Authors: Cavini, I.A. Winter, A.J. D'Muniz Pereira, H. Woolfson, D.N. Crump, M.P. Garratt, R.C. Tags: coiled coils hendecad repeats heterodimerization metastability septins research papers Source Type: research
Crystal structures of human and mouse ketohexokinase provide a structural basis for species- and isoform-selective inhibitor design
A molecular understanding of the proteins involved in fructose metabolism is essential for controlling the current spread of fructose-related obesity, diabetes and related adverse metabolic states in Western populations. Fructose catabolism starts with the phosphorylation of d-fructose to fructose 1-phosphate by ketohexokinase (KHK). KHK exists in two alternatively spliced isoforms: the hepatic and intestinal isoform KHK-C and the peripheral isoform KHK-A. Here, the structure of apo murine KHK (mKHK), which differs from structures of human KHK in overall conformation, is reported. An isoform-selective ligand, which offers ...
Source: Acta Crystallographica Section D - September 15, 2023 Category: Biochemistry Authors: Ebenhoch, R. Bauer, M. Romig, H. Gottschling, D. Kley, J.T. Heine, N. Weber, A. Uphues, I. Nar, H. Pautsch, A. Tags: human ketohexokinase mouse ketohexokinase inhibitors isoform selectivity fructose metabolism structure-based design research papers Source Type: research
Predicted models and CCP4
In late 2020, the results of CASP14, the 14th event in a series of competitions to assess the latest developments in computational protein structure-prediction methodology, revealed the giant leap forward that had been made by Google's Deepmind in tackling the prediction problem. The level of accuracy in their predictions was the first instance of a competitor achieving a global distance test score of better than 90 across all categories of difficulty. This achievement represents both a challenge and an opportunity for the field of experimental structural biology. For structure determination by macromolecular X-ray crystal...
Source: Acta Crystallographica Section D - August 18, 2023 Category: Biochemistry Authors: Simpkin, A.J. Caballero, I. McNicholas, S. Stevenson, K. Jim é nez, E. S á nchez Rodr í guez, F. Fando, M. Uski, V. Ballard, C. Chojnowski, G. Lebedev, A. Krissinel, E. Us ó n, I. Rigden, D.J. Keegan, R.M. Tags: CCP4 predicted models molecular replacement macromolecular crystallography structure determination research papers Source Type: research
A Python package based on robust statistical analysis for serial crystallography data processing
The term robustness in statistics refers to methods that are generally insensitive to deviations from model assumptions. In other words, robust methods are able to preserve their accuracy even when the data do not perfectly fit the statistical models. Robust statistical analyses are particularly effective when analysing mixtures of probability distributions. Therefore, these methods enable the discretization of X-ray serial crystallography data into two probability distributions: a group comprising true data points (for example the background intensities) and another group comprising outliers (for example Bragg peaks or ba...
Source: Acta Crystallographica Section D - August 16, 2023 Category: Biochemistry Authors: Hadian-Jazi, M. Sadri, A. Tags: RGFlib robust statistics serial crystallography robust peak-finding robust bad pixel mask making research papers Source Type: research
Correcting systematic errors in diffraction data with modern scaling algorithms
X-ray diffraction enables the routine determination of the atomic structure of materials. Key to its success are data-processing algorithms that allow experimenters to determine the electron density of a sample from its diffraction pattern. Scaling, the estimation and correction of systematic errors in diffraction intensities, is an essential step in this process. These errors arise from sample heterogeneity, radiation damage, instrument limitations and other aspects of the experiment. New X-ray sources and sample-delivery methods, along with new experiments focused on changes in structure as a function of perturbations...
Source: Acta Crystallographica Section D - August 16, 2023 Category: Biochemistry Authors: Aldama, L.A. Dalton, K.M. Hekstra, D.R. Tags: X-ray crystallography scaling variational inference deep learning topical reviews Source Type: research
Novel starting points for fragment-based drug design against mycobacterial thioredoxin reductase identified using crystallographic fragment screening
The increasing number of people dying from tuberculosis and the existence of extensively drug-resistant strains has led to an urgent need for new antituberculotic drugs with alternative modes of action. As part of the thioredoxin system, thioredoxin reductase (TrxR) is essential for the survival of Mycobacterium tuberculosis (Mtb) and shows substantial differences from human TrxR, making it a promising and most likely selective target. As a model organism for Mtb, crystals of Mycobacterium smegmatis TrxR that diffracted to high resolution were used in crystallographic fragment screening to discover binding fragments and ne...
Source: Acta Crystallographica Section D - August 14, 2023 Category: Biochemistry Authors: F ü sser, F.T. Wollenhaupt, J. Weiss, M.S. K ü mmel, D. Koch, O. Tags: crystallographic fragment screening Mycobacterium tuberculosis Mycobacterium smegmatis thioredoxin reductase antituberculotic drugs research papers Source Type: research
Raimond B. G. Ravelli (25 March 1968 – 30 June 2023)
(Source: Acta Crystallographica Section D)
Source: Acta Crystallographica Section D - August 10, 2023 Category: Biochemistry Authors: Garman, E.F. Tags: obituaries Raimond B. G. Ravelli Source Type: research
LifeSoaks: a tool for analyzing solvent channels in protein crystals and obstacles for soaking experiments
Due to the structural complexity of proteins, their corresponding crystal arrangements generally contain a significant amount of solvent-occupied space. These areas allow a certain degree of intracrystalline protein flexibility and mobility of solutes. Therefore, knowledge of the geometry of solvent-filled channels and cavities is essential whenever the dynamics inside a crystal are of interest. Especially in soaking experiments for structure-based drug design, ligands must be able to traverse the crystal solvent channels and reach the corresponding binding pockets. Unsuccessful screenings are sometimes attributed to the g...
Source: Acta Crystallographica Section D - August 10, 2023 Category: Biochemistry Authors: Pletzer-Zelgert, J. Ehrt, C. Fender, I. Griewel, A. Flachsenberg, F. Klebe, G. Rarey, M. Tags: solvent channels soaking LifeSoaks Voronoi diagram structure-based drug design research papers Source Type: research
Structural basis of the amidase ClbL central to the biosynthesis of the genotoxin colibactin
Colibactin is a genotoxic natural product produced by select commensal bacteria in the human gut microbiota. The compound is a bis-electrophile that is predicted to form interstrand DNA cross-links in target cells, leading to double-strand DNA breaks. The biosynthesis of colibactin is carried out by a mixed NRPS – PKS assembly line with several noncanonical features. An amidase, ClbL, plays a key role in the pathway, catalyzing the final step in the formation of the pseudodimeric scaffold. ClbL couples α -aminoketone and β -ketothioester intermediates attached to separate carrier domains on the NRPS – PKS assembly. H...
Source: Acta Crystallographica Section D - August 10, 2023 Category: Biochemistry Authors: Tripathi, P. Mousa, J.J. Guntaka, N.S. Bruner, S.D. Tags: natural product biosynthesis amidases colibactin ClbL microbiome research papers Source Type: research
Announcing the launch of Protein Data Bank China as an Associate Member of the Worldwide Protein Data Bank Partnership
The Protein Data Bank (PDB) is the single global archive of atomic-level, three-dimensional structures of biological macromolecules experimentally determined by macromolecular crystallography, nuclear magnetic resonance spectroscopy or three-dimensional cryo-electron microscopy. The PDB is growing continuously, with a recent rapid increase in new structure depositions from Asia. In 2022, the Worldwide Protein Data Bank (wwPDB; https://www.wwpdb.org/) partners welcomed Protein Data Bank China (PDBc; https://www.pdbc.org.cn) to the organization as an Associate Member. PDBc is based in the National Facility for Protein Scienc...
Source: Acta Crystallographica Section D - August 10, 2023 Category: Biochemistry Authors: Xu, W. Velankar, S. Patwardhan, A. Hoch, J.C. Burley, S.K. Kurisu, G. Tags: macromolecular crystallography nuclear magnetic resonance three-dimensional cryo-electron microscopy Protein Data Bank Biological Magnetic Resonance Bank Electron Microscopy Data Bank Worldwide Protein Data Bank letters to the editor Source Type: research
Rhizobium etli has two l-asparaginases with low sequence identity but similar structure and catalytic center
The genome of Rhizobium etli, a nitrogen-fixing bacterial symbiont of legume plants, encodes two l-asparaginases, ReAIV and ReAV, that have no similarity to the well characterized enzymes of class 1 (bacterial type) and class 2 (plant type). It has been hypothesized that ReAIV and ReAV might belong to the same structural class 3 despite their low level of sequence identity. When the crystal structure of the inducible and thermolabile protein ReAV was solved, this hypothesis gained a stronger footing because the key residues of ReAV are also present in the sequence of the constitutive and thermostable ReAIV protein. High-re...
Source: Acta Crystallographica Section D - July 26, 2023 Category: Biochemistry Authors: Loch, J.I. Worsztynowicz, P. Sliwiak, J. Grzechowiak, M. Imiolczyk, B. Pokrywka, K. Chwastyk, M. Gilski, M. Jaskolski, M. Tags: l-asparaginases Rhizobium etli zinc-binding proteins enzymatic mechanism occluded water molecules amidohydrolases structural homology enzyme kinetics research papers Source Type: research
A standard descriptor for fixed-target serial crystallography
Fixed-target crystallography has become a widely used approach for serial crystallography at both synchrotron and X-ray free-electron laser (XFEL) sources. A plethora of fixed targets have been developed at different facilities and by various manufacturers, with different characteristics and dimensions and with little or no emphasis on standardization. These many fixed targets have good reasons for their design, shapes, fabrication materials and the presence or absence of apertures and fiducials, reflecting the diversity of serial experiments. Given this, it would be a Sisyphean task to design and manufacture a new standar...
Source: Acta Crystallographica Section D - July 18, 2023 Category: Biochemistry Authors: Owen, R.L. de Sanctis, D. Pearson, A.R. Beale, J.H. Tags: fixed targets serial crystallography standardization letters to the editor Source Type: research
