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
N1 - Funding Information:
We thank N. Kanoh, H. Aono, T. Yoshimura, Y. Fukushima, H. Miyatake and Y. Kondoh for suggestions; M. Muroi and H. Kondo for technical assistance with the LC-MS/MS analysis; T. Nakamura and Y. Hongo for mass spectrometry (RIKEN); R. Nakazawa for DNA sequencing (RIKEN); and the Support Unit for Bio-material Analysis, RIKEN BSI Research Resources Center, and K. Fukumoto for DNA microarray analysis. The synchrotron radiation experiments were performed at BL26B2 in SPring-8 with the Mail-in data collection system with the approval of RIKEN (Proposal No. 20090085). This study was supported in part by a Grant-in-Aid from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (MEXT).
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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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 -