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Biological Chemistry

Calixarenes Roam Protein’s Surface

Ring-shaped molecules could promote crystallization

by Carmen Drahl
May 7, 2012 | A version of this story appeared in Volume 90, Issue 19

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Credit: Nature Chem.
A calixarene (stick) binds to the surface of the cytochrome c protein (space fill).
In this crystal structure, a calixarene (stick) binds to the surface of cytochrome c (spacefill)
Credit: Nature Chem.
A calixarene (stick) binds to the surface of the cytochrome c protein (space fill).
PROTEIN CAMO
Credit: Adapted from Nat. Chem.
This animation depicts how a calixarene might explore, and effectively camouflage, cytochrome c’s surface.

The first complete structural analysis of a protein complexed with a cup-shaped calixarene molecule reveals that the pairing is dynamic, with the calixarene interacting at multiple binding sites (Nat. Chem., DOI: 10.1038/nchem.1342). That insight could someday help control protein interactions involved in drug or biosensor development. Researchers have long sought small molecules to disguise protein surfaces and in effect modify their interaction properties. Despite calixarenes’ potential for this job, researchers lacked details about how the molecules interact with protein surfaces. Graduate student Róise E. McGovern and Peter B. Crowley of the National University of Ireland, Galway, along with colleagues, used NMR and X-ray crystallography to study how p-sulfonatocalix[4]arene binds to lysine-rich cytochrome c, a stand-in for histones, which regulate gene expression and are a potential target of protein-surface-binding agents. The NMR and X-ray data were in close agreement and suggested the calixarene explores the protein surface by binding to three or more lysine side chains. The team created an animation to depict its possible motion. Masking lysines is an established trick for coaxing protein crystallization, another potential calixarene application, according to the researchers.

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