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Calixarene docks dimethyllysine on lysozyme

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p-Sulfonatocalix[4]arene selectively encapsulates Lys116-Me2 on dimethylated lysozyme, mimicking an aromatic cage.

Source

Structural study of a small molecule receptor bound to dimethyllysine in lysozyme

McGovern RE, Snarr BD, Lyons JA, et al. · Chemical science · 2015

doi.org/10.1039/c4sc02383hRead the full paper ↗49 citationscc by

Study at a glance

Design
Other — Crystal and NMR study of p-sulfonatocalix[4]arene bound to dimethylated lysozyme lysines
N
Protein–small-molecule structural study — no cohort N
Population
Dimethylated hen egg-white lysozyme with sclx4
Outcome
Site-selective Lys-Me2 encapsulation by the calixarene

Structured fields used in claim comparison tables when every cited study has a complete layer.

What they did

Authors dimethylated hen lysozyme, solved sclx4 co-crystal structures, used 1H/13C NMR chemical shifts, and ran short MD at each Lys-Me2 site.

What they found

Lys116-Me2 is encapsulated in the calixarene; NMR shows a large upfield NεMe shift; accessibility and nearby Arg/Asn contacts explain selectivity versus other lysines.

The limits

What it doesn't show

No histone-tail co-crystal; MM-PBSA could not rank sites; precipitation limited solution stoichiometry.

Key terms

Dimethyllysine (KMe2)
Lysine post-translational methylation that creates a cation for aromatic-cage recognition.
p-Sulfonatocalix[4]arene (sclx4)
Anionic bowl-shaped receptor used as a synthetic lysine binder.
Cation–π interaction
Attraction between a cation (here NMe2) and aromatic faces of the calixarene.
Aromatic cage
Protein motif (e.g. chromodomain) that binds methyllysine with aromatics.
Accessible surface area (ASA)
Solvent-exposed area used to rank lysine steric accessibility.

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Quiz yourself

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Preferred dimethyllysine on lysozyme:

Common questions

Which lysine is selected?

Lys116-Me2, the most projecting dimethyllysine.

What NMR signature marks binding?

Large upfield shift of Lys116-Me2 NεMe at ~2.92 ppm.

What drives binding?

Cation–π plus hydrophobic cavity occupancy, not mainly salt bridges.

Why not other lysines?

Lower steric accessibility; MD shows Arg/Asn contacts unique to Lys116.

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