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dc.contributor.authorMcGovern, Róise E.
dc.contributor.authorSnarr, Brendan D.
dc.contributor.authorLyons, Joseph A.
dc.contributor.authorMcFarlane, James
dc.contributor.authorWhiting, Amanda L.
dc.contributor.authorPaci, Irina
dc.contributor.authorHof, Fraser
dc.contributor.authorCrowley, Peter B.
dc.date.accessioned2018-09-20T16:17:08Z
dc.date.available2018-09-20T16:17:08Z
dc.date.issued2015-01-01
dc.identifier.citationMcGovern, Róise E. Snarr, Brendan D.; Lyons, Joseph A.; McFarlane, James; Whiting, Amanda L.; Paci, Irina; Hof, Fraser; Crowley, Peter B. (2015). Structural study of a small molecule receptor bound to dimethyllysine in lysozyme. Chem. Sci. 6 (1), 442-449
dc.identifier.issn2041-6520,2041-6539
dc.identifier.urihttp://hdl.handle.net/10379/12791
dc.description.abstractLysine is a ubiquitous residue on protein surfaces. Post translational modifications of lysine, including methylation to the mono-, di- or trimethylated amine result in chemical and structural alterations that have major consequences for protein interactions and signalling pathways. Small molecules that bind to methylated lysines are potential tools to modify such pathways. To make progress in this direction, detailed structural data of ligands in complex with methylated lysine is required. Here, we report a crystal structure of p-sulfonatocalix[4] arene (sclx(4)) bound to methylated lysozyme in which the lysine residues were chemically modified from Lys-NH3+ to Lys-NH(Me-2)(+)Of the six possible dimethyllysine sites, sclx4 selected Lys116-Me-2 and the dimethylamino substituent was deeply buried in the calixarene cavity. This complex confirms the tendency for Lys-Me-2 residues to form cation-pi interactions, which have been shown to be important in protein recognition of histone tails bearing methylated lysines. Supporting data from NMR spectroscopy and MD simulations confirm the selectivity for Lys116-Me-2 in solution. The structure presented here may serve as a stepping stone to the development of new biochemical reagents that target methylated lysines.
dc.publisherRoyal Society of Chemistry (RSC)
dc.relation.ispartofChem. Sci.
dc.subjectegg-white lysozyme
dc.subjectepigenetic reader protein
dc.subjectmodified histone tail
dc.subjectsynthetic receptor
dc.subjectlysine methylation
dc.subjectmacromolecular crystallography
dc.subjectsupramolecular hosts
dc.subjectcytochrome-c
dc.subjectrecognition
dc.subjectbinding
dc.titleStructural study of a small molecule receptor bound to dimethyllysine in lysozyme
dc.typeArticle
dc.identifier.doi10.1039/c4sc02383h
dc.local.publishedsourcehttp://pubs.rsc.org/en/content/articlepdf/2015/sc/c4sc02383h
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