Pradimicin-resistance of yeast is caused by a point mutation of the histidine-containing phosphotransfer protein Ypd1.

Fumitaka Hiramoto, Nobuhiko Nomura, Tamotsu Furumai, Yasuhiro Igarashi, Toshikazu Oki

Biotechnology Research Center, Toyama Prefectural University, 5180, Kurokawa, Kosugi, Toyama 939-0398, Japan.

The Journal of antibiotics 2003 Dec

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Pradimicin is an antifungal antibiotic which induces apoptosis like cell death in the yeast Saccharomyces cerevisiae. Pradimicin-resistant mutants were isolated from the S. cerevisiae and the mutation points were analyzed. A point mutation of YPD1 that led to a substitution of the 74th glycine (Gly74) to cysteine (Cys) was identified in a mutant strain NH1. In S. cerevisiae, Ypd1 transfers a phosphoryl group from the sensor kinase Slnl to the response regulator Sskl which regulates a downstream MAP kinase in response to hyperosmotic stress. Gly74 is located in a three-residue reverse turn domain that connects two alpha-helices, one of which contains a histidine residue which is phosphorylated. In the reverse turn, glycine (relative position +10 to the active-site histidine) is highly conserved in Ypd1 and other histidine-containing phosphotransfer proteins. It was therefore suggested that the substitution of Gly74 to Cys altered the Ypd1 structure, which resulted in the resistance to pradimicin.

Citation

Fumitaka Hiramoto, Nobuhiko Nomura, Tamotsu Furumai, Yasuhiro Igarashi, Toshikazu Oki. Pradimicin-resistance of yeast is caused by a point mutation of the histidine-containing phosphotransfer protein Ypd1. The Journal of antibiotics. 2003 Dec;56(12):1053-7