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dc.contributor.authorKalia, Munishikha
dc.contributor.authorKukol, A.
dc.date.accessioned2016-03-03T10:33:45Z
dc.date.available2016-03-03T10:33:45Z
dc.date.issued2011
dc.identifier.citationKalia , M & Kukol , A 2011 , ' Structure and dynamics of the kinase IKK-β – A key regulator of the NF-kappa B transcription factor ' , Journal of Structural Biology , vol. 176 , no. 2 , pp. 133-142 . https://doi.org/10.1016/j.jsb.2011.07.012
dc.identifier.issn1047-8477
dc.identifier.otherPURE: 406940
dc.identifier.otherPURE UUID: b5728d99-3591-4c0d-945f-88c606a2f277
dc.identifier.otherScopus: 80053383983
dc.identifier.urihttp://hdl.handle.net/2299/16622
dc.description'This is the author's version of a work that was accepted for publication in Journal of Structural Biology. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Journal of Structural Biology, 176 (2) (2011) DOI 10.1016/j.jsb.2011.07.012'
dc.description.abstractThe inhibitor κB kinase-β (IKK-β) phosphorylates the NF-κB inhibitor protein IκB leading to the translocation of the transcription factor NF-κB to the nucleus. The transcription factor NF-κB and consequently IKK-β are central to signal transduction pathways of mammalian cells. The purpose of this research was to develop a 3D structural model of the IKK-β kinase domain with its ATP cofactor and investigate its dynamics and ligand binding potential. Through a combination of comparative modelling and simulated heating/annealing molecular dynamics (SAMD) simulation in explicit water the model accuracy could be substantially improved compared to comparative modelling on its own as shown by model validation measures. The structure revealed the details of ATP/Mg2+ binding indicating hydrophobic interactions with the adenine base and a significant contribution of Mg2+ as a bridge between ATP phosphate groups and negatively charged side chains. The molecular dynamics trajectories of the ATP-bound and free enzyme showed two conformations in each case, which contributed to the majority of the trajectory. The ATP-free enzyme revealed a novel binding site distant from the ATP binding site that was not encountered in the ATP bound enzyme. Based on the overall structural flexibility, it is suggested that a truncated version of the kinase domain from Ala14 to Leu265 should be subjected to crystallisation trials. The 3D structure of this enzyme will enable rational design of new ligands and analysis of protein–protein interactions. Furthermore, our results may provide a new impetus for wet-lab based structural investigation focussing on a truncated kinase domain.en
dc.language.isoeng
dc.relation.ispartofJournal of Structural Biology
dc.rightsOpen
dc.subjectprotein kinase
dc.subjectprotein structure
dc.subjectcomparative modelling
dc.subjectmolecular dynamics
dc.subjectbinding site
dc.titleStructure and dynamics of the kinase IKK-β – A key regulator of the NF-kappa B transcription factoren
dc.contributor.institutionDepartment of Human and Environmental Sciences
dc.contributor.institutionHealth & Human Sciences Research Institute
dc.contributor.institutionSchool of Life and Medical Sciences
dc.contributor.institutionAgriculture, Food and Veterinary Sciences
dc.contributor.institutionPharmacology and Clinical Science Research
dc.contributor.institutionCardiovascular Pathologies
dc.contributor.institutionBiochemistry and Bioinformatics
dc.contributor.institutionMolecular Biology, Microbiology and Biosciences
dc.contributor.institutionBiosciences Research Group
dc.description.statusPeer reviewed
dc.identifier.urlhttp://www.scopus.com/inward/record.url?scp=80053383983&partnerID=8YFLogxK
dc.relation.schoolSchool of Life and Medical Sciences
dc.description.versiontypeFinal Accepted Version
dcterms.dateAccepted2011
rioxxterms.versionAM
rioxxterms.versionofrecordhttps://doi.org/10.1016/j.jsb.2011.07.012
rioxxterms.typeJournal Article/Review
herts.preservation.rarelyaccessedtrue
herts.rights.accesstypeOpen


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