Structural highlights
Function
[BLH1_YEAST] The normal physiological role of the enzyme is unknown, but it is not essential for the viability of yeast cells. Has aminopeptidase activity, shortening substrate peptides sequentially by 1 amino acid. Has bleomycin hydrolase activity, which can protect the cell from the toxic effects of bleomycin. Has homocysteine-thiolactonase activity, protecting the cell against homocysteine toxicity. Acts as a repressor in the GAL4 regulatory system, but this does not require either the peptidase or nucleic acid-binding activities.[1] [2]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
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.
Crystal structure of a conserved protease that binds DNA: the bleomycin hydrolase, Gal6.,Joshua-Tor L, Xu HE, Johnston SA, Rees DC Science. 1995 Aug 18;269(5226):945-50. PMID:7638617[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Wang H, Ramotar D. Cellular resistance to bleomycin in Saccharomyces cerevisiae is not affected by changes in bleomycin hydrolase levels. Biochem Cell Biol. 2002;80(6):789-96. PMID:12555812
- ↑ Zimny J, Sikora M, Guranowski A, Jakubowski H. Protective mechanisms against homocysteine toxicity: the role of bleomycin hydrolase. J Biol Chem. 2006 Aug 11;281(32):22485-92. Epub 2006 Jun 12. PMID:16769724 doi:http://dx.doi.org/M603656200
- ↑ Joshua-Tor L, Xu HE, Johnston SA, Rees DC. Crystal structure of a conserved protease that binds DNA: the bleomycin hydrolase, Gal6. Science. 1995 Aug 18;269(5226):945-50. PMID:7638617
