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Science 18 August 1995:
Vol. 269. no. 5226, pp. 945 - 950
DOI: 10.1126/science.7638617
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Articles

Science, Vol 269, Issue 5226, 945-950
Copyright © 1995 by American Association for the Advancement of Science

articles

Crystal structure of a conserved protease that binds DNA: the bleomycin hydrolase, Gal6

L Joshua-Tor, HE Xu, SA Johnston, and DC Rees

Divison of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena 91125, USA.

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 A 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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