Abstract
The discovery of small molecules that bind to a specific target and disrupt the function of proteins is an important step in chemical biology, especially for poorly characterized proteins. Human pirin is a nuclear protein of unknown function that is widely expressed in punctate subnuclear structures in human tissues. Here, we report the discovery of a small molecule that binds to pirin. We determined how the small molecule bound to pirin by solving the cocrystal structure. Either knockdown of pirin or treatment with the small molecule inhibited melanoma cell migration. Thus, inhibition of pirin by the small molecule has led to a greater understanding of the function of pirin and represents a new method of studying pirin-mediated signaling pathways.
| Original language | English |
|---|---|
| Pages (from-to) | 667-673 |
| Number of pages | 7 |
| Journal | Nature Chemical Biology |
| Volume | 6 |
| Issue number | 9 |
| DOIs | |
| Publication status | Published - 2010 Sep |
| Externally published | Yes |
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ASJC Scopus subject areas
- Cell Biology
- Molecular Biology
- Medicine(all)
Cite this
A small-molecule inhibitor shows that pirin regulates migration of melanoma cells. / Miyazaki, Isao; Simizu, Siro; Okumura, Hideo; Takagi, Satoshi; Osada, Hiroyuki.
In: Nature Chemical Biology, Vol. 6, No. 9, 09.2010, p. 667-673.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - A small-molecule inhibitor shows that pirin regulates migration of melanoma cells
AU - Miyazaki, Isao
AU - Simizu, Siro
AU - Okumura, Hideo
AU - Takagi, Satoshi
AU - Osada, Hiroyuki
PY - 2010/9
Y1 - 2010/9
N2 - The discovery of small molecules that bind to a specific target and disrupt the function of proteins is an important step in chemical biology, especially for poorly characterized proteins. Human pirin is a nuclear protein of unknown function that is widely expressed in punctate subnuclear structures in human tissues. Here, we report the discovery of a small molecule that binds to pirin. We determined how the small molecule bound to pirin by solving the cocrystal structure. Either knockdown of pirin or treatment with the small molecule inhibited melanoma cell migration. Thus, inhibition of pirin by the small molecule has led to a greater understanding of the function of pirin and represents a new method of studying pirin-mediated signaling pathways.
AB - The discovery of small molecules that bind to a specific target and disrupt the function of proteins is an important step in chemical biology, especially for poorly characterized proteins. Human pirin is a nuclear protein of unknown function that is widely expressed in punctate subnuclear structures in human tissues. Here, we report the discovery of a small molecule that binds to pirin. We determined how the small molecule bound to pirin by solving the cocrystal structure. Either knockdown of pirin or treatment with the small molecule inhibited melanoma cell migration. Thus, inhibition of pirin by the small molecule has led to a greater understanding of the function of pirin and represents a new method of studying pirin-mediated signaling pathways.
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UR - http://www.scopus.com/inward/citedby.url?scp=77955924828&partnerID=8YFLogxK
U2 - 10.1038/nchembio.423
DO - 10.1038/nchembio.423
M3 - Article
C2 - 20711196
AN - SCOPUS:77955924828
VL - 6
SP - 667
EP - 673
JO - Nature Chemical Biology
JF - Nature Chemical Biology
SN - 1552-4450
IS - 9
ER -