4N0J

Crystal structure of dimethyllysine hen egg-white lysozyme in complex with sclx4 at 1.9 A resolution

Summary for 4N0J

• Entry DOI: 10.2210/pdb4n0j/pdb
• Related: 4IPQ 4IPR
• Descriptor: Lysozyme C, 25,26,27,28-tetrahydroxypentacyclo[19.3.1.1~3,7~.1~9,13~.1~15,19~]octacosa-1(25),3(28),4,6,9(27),10,12,15(26),16,18,21,23-dodecaene-5,11,17,23-tetrasulfonic acid, CHLORIDE ION, ... (7 entities in total)
• Functional Keywords: hydrolase (o-glycosyl), hydrolase
• Biological source: Gallus gallus (bantam,chickens)
• Cellular location: Secreted: P00698
• Total number of polymer chains: 2
• Total formula weight: 32660.37

Authors

McGovern, R.E.,Crowley, P.B. (deposition date: 2013-10-02, release date: 2014-11-12, Last modification date: 2023-09-20)

Primary citation

McGovern, R.E.,Snarr, B.D.,Lyons, J.A.,McFarlane, J.,Whiting, A.L.,Paci, I.,Hof, F.,Crowley, P.B.
Structural study of a small molecule receptor bound to dimethyllysine in lysozyme.
Chem Sci, 6:442-449, 2015

PubMed Abstract: Lysine 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 -sulfonatocalix[4]arene (sclx) bound to methylated lysozyme in which the lysine residues were chemically modified from Lys-NH to Lys-NH(Me). Of the six possible dimethyllysine sites, sclx selected Lys116-Me and the dimethylamino substituent was deeply buried in the calixarene cavity. This complex confirms the tendency for Lys-Me residues to form cation-π 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 in solution. The structure presented here may serve as a stepping stone to the development of new biochemical reagents that target methylated lysines.

PubMed: 25530835
DOI: 10.1039/C4SC02383H

Experimental method

X-RAY DIFFRACTION (1.9 Å)