Biochemistry

More than one way to target a protein

+ See all authors and affiliations

Science  01 Jan 2016:
Vol. 351, Issue 6268, pp. 38
DOI: 10.1126/science.351.6268.38-b

Proteins have multiple binding sites that may contribute to their regulation

CREDIT: LUDLOW ET AL., PNAS (9 NOVEMBER 2015) © NATIONAL ACADEMY OF SCIENCES

The primary function of many proteins involves binding to another protein or small molecule. In some cases, however, a second molecule interacting with a distinct site on the protein regulates this primary binding. To identify such functional secondary sites, Ludlow et al. used x-ray crystallography to screen a library of molecules to detect binding to 24 protein targets. Two-thirds of the proteins had at least two binding sites. Sequence analysis of secondary sites showed that most were evolutionarily conserved, suggesting biological function. Moreover, their physicochemical properties indicated that secondary sites may be druggable. Targeting these sites could provide a way to increase protein activity in a therapeutically advantageous manner.

Proc. Natl. Acad. Sci. U.S.A. 10.1073/pnas.1518946112 (2015).

Related Content

Navigate This Article