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dc.contributor.authorPflug, Alexander
dc.contributor.authorJohnson, Kenneth
dc.contributor.authorEngh, Richard Alan
dc.date.accessioned2012-11-30T10:29:04Z
dc.date.available2012-11-30T10:29:04Z
dc.date.issued2012
dc.description.abstractWith its ability to show the interactions between drug-target proteins and small-molecule ligands, X-ray crystallography is an essential tool in drug-discovery programmes. However, its usefulness can be limited by crystallization artifacts or by the data resolution, and in particular when assumptions of unimodal binding (and isotropic motion) do not apply. Discrepancies between the modelled crystal structure and the physiological range of structures generally prevent quantitative estimation of binding energies. Improved crystal structure resolution will often not aid energy estimation because the conditions which provide the highest rigidity and resolution are not likely to reflect physiological conditions. Instead, strategies must be employed to measure and model flexibility and multiple binding modes to supplement crystallographic information. One useful tool is the use of anomalous dispersion for small molecules that contain suitable atoms. Here, an analysis of the binding of the kinase inhibitor H-89 to protein kinase A (PKA) is presented. H-89 contains a bromobenzene moiety that apparently binds with multiple conformations in the kinase ATP pocket. Using anomalous dispersion methods, it was possible to resolve these conformations into two distinct binding geometries.en
dc.descriptionThis article is part of Alexander Pflugs' doctoral thesis, available in Munin at <a href=http://hdl.handle.net/10037/4145>http://hdl.handle.net/10037/4145</a>en
dc.identifier.citationActa Crystallographica. Section F : Structural Biology and Crystallization Communications 68(2012) s. 873-877en
dc.identifier.cristinIDFRIDAID 965489
dc.identifier.doidoi: 10.1107/S1744309112028655
dc.identifier.issn1744-3091
dc.identifier.urihttps://hdl.handle.net/10037/4645
dc.identifier.urnURN:NBN:no-uit_munin_4360
dc.language.isoengen
dc.publisherBlackwell Munksgaarden
dc.rights.accessRightsopenAccess
dc.subjectVDP::Mathematics and natural science: 400::Basic biosciences: 470::Molecular biology: 473en
dc.subjectVDP::Matematikk og Naturvitenskap: 400::Basale biofag: 470::Molekylærbiologi: 473en
dc.titleAnomalous dispersion analysis of inhibitor flexibility : a case study of the kinase inhibitor H-89en
dc.typeJournal articleen
dc.typeTidsskriftartikkelen
dc.typePeer revieweden


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