CRYSTAL-STRUCTURE OF A CONSERVED PROTEASE THAT BINDS DNA - THE BLEOMYCIN HYDROLASE, GAL6

被引:117
作者
JOSHUATOR, L
XU, HE
JOHNSTON, SA
REES, DC
机构
[1] CALTECH, DIV CHEM & CHEM ENGN, 147-75CH, PASADENA, CA 91125 USA
[2] UNIV TEXAS, SW MED CTR, DEPT MED, DALLAS, TX 75235 USA
[3] UNIV TEXAS, SW MED CTR, DEPT BIOCHEM, DALLAS, TX 75235 USA
关键词
D O I
10.1126/science.7638617
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Bleomycin hydrolase is a cysteine protease that hydrolyzes the anticancer drug bleomycin. The homolog in yeast, Gal6, has recently been identified and found to bind DNA and to act as a repressor in the Gal4 regulatory system, The crystal structure of Gal6 at 2.2 Angstrom resolution reveals a hexameric structure with a prominent central channel, The papain-like active sites are situated within the central channel, in a manner resembling the organization of active sites in the proteasome. The Gal6 channel is lined with 60 lysine residues from the six subunits, suggesting a role in DNA binding, The carboxyl-terminal arm of Gal6 extends into the active site cleft and may serve a regulatory function. Rather than each residing in distinct, separable domains, the protease and DNA-binding activities appear structurally intertwined in the hexamer, implying a coupling of these two activities.
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页码:945 / 950
页数:6
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