ArticleActa crystallographica. Section D, Biological crystallography2014
Ensemble refinement shows conformational flexibility in crystal structures of human complement factor D.
Article in Acta crystallographica. Section D, Biological crystallography, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed.
- Article
- Innovative Strategies in X-ray Crystallography for Exploring Structural Dynamics and Reaction Mechanisms in Metabolic Disorders.Journal of personalized medicine · 2024Review
- Structural dynamics and functional cooperativity of human NQO1 by ambient temperature serial crystallography and simulations.Protein science : a publication of the Protein Society · 2024Article
- Conformational dynamics of adenylate kinase in crystals.Structural dynamics (Melville, N.Y.) · 2024Article
- Role of complement factor D in cardiovascular and metabolic diseases.Frontiers in immunology · 2024Review
- New TSPO Crystal Structures of Mutant and Heme-Bound Forms with Altered Flexibility, Ligand Binding, and Porphyrin Degradation Activity.Biochemistry · 2023Article
- Refinement of multiconformer ensemble models from multi-temperature X-ray diffraction data.Methods in enzymology · 2023Article
- Mechanistic basis of GPCR activation explored by ensemble refinement of crystallographic structures.Protein science : a publication of the Protein Society · 2022Article
- Functional Identification of Complement Factor D and Analysis of Its Expression during GCRV Infection in Grass Carp (International journal of molecular sciences · 2021Article
- Uncovering Membrane-Bound Models of Coagulation Factors by Combined Experimental and Computational Approaches.Thrombosis and haemostasis · 2021Review
- Exploring ligand dynamics in protein crystal structures with ensemble refinement.Acta crystallographica. Section D, Structural biology · 2021Article
- Complement Factor D as a Strategic Target for Regulating the Alternative Complement Pathway.Frontiers in immunology · 2021Review
- Unique active-site and subsite features in the arabinogalactan-degrading GH43 exo-β-1,3-galactanase fromThe Journal of biological chemistry · 2020Article
- Discovery of allosteric binding sites by crystallographic fragment screening.Current opinion in structural biology · 2020Review
- Substrate-recognition mechanism of tomato β-galactosidase 4 using X-ray crystallography and docking simulation.Planta · 2020Article
- Mechanistic and Crystallographic Studies of Azoreductase AzoA fromACS chemical biology · 2020Article
- Allostery in Coagulation Factor VIIa Revealed by Ensemble Refinement of Crystallographic Structures.Biophysical journal · 2019Article
- Discovery and Design of First Benzylamine-Based Ligands Binding to an Unlocked Conformation of the Complement Factor D.ACS medicinal chemistry letters · 2018Article
- Article
- Integrating Experiment and Theory to Understand TCR-pMHC Dynamics.Frontiers in immunology · 2018Review
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3 authors.
Funding
Abstract
Human factor D (FD) is a self-inhibited thrombin-like serine proteinase that is critical for amplification of the complement immune response. FD is activated by its substrate through interactions outside the active site. The substrate-binding, or `exosite', region displays a well defined and rigid conformation in FD. In contrast, remarkable flexibility is observed in thrombin and related proteinases, in which Na(+) and ligand binding is implied in allosteric regulation of enzymatic activity through protein dynamics. Here, ensemble refinement (ER) of FD and thrombin crystal structures is used to evaluate structure and dynamics simultaneously. A comparison with previously published NMR data for thrombin supports the ER analysis. The R202A FD variant has enhanced activity towards artificial peptides and simultaneously displays active and inactive conformations of the active site. ER revealed pronounced disorder in the exosite loops for this FD variant, reminiscent of thrombin in the absence of the stabilizing Na(+) ion. These data indicate that FD exhibits conformational dynamics like thrombin, but unlike in thrombin a mechanism has evolved in FD that locks the unbound native state into an ordered inactive conformation via the self-inhibitory loop. Thus, ensemble refinement of X-ray crystal structures may represent an approach alternative to spectroscopy to explore protein dynamics in atomic detail.
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