Pradimicin-resistance of yeast is caused by a point mutation of the histidine-containing phosphotransfer protein Ypd1.
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.
Hiramoto
Fumitaka
F
Biotechnology Research Center, Toyama Prefectural University, 5180, Kurokawa, Kosugi, Toyama 939-0398, Japan.
Nomura
Nobuhiko
N
Furumai
Tamotsu
T
Igarashi
Yasuhiro
Y
Oki
Toshikazu
T
D018943:Anthracyclines / Q000737:chemistry / Q000494:pharmacology*; D001483:Base Sequence; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000235:genetics*; D025141:Drug Resistance, Fungal; D047908:Intracellular Signaling Peptides and Proteins; D017354:Point Mutation; D011494:Protein Kinases; D012441:Saccharomyces cerevisiae / Q000187:drug effects*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics*; D000095643:Pradimicins and Benanomicins
D018943:Anthracyclines; D017931:DNA Primers; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D011494:Protein Kinases; D029701:Saccharomyces cerevisiae Proteins; C058036:pradimicin A; D000095643:Pradimicins and Benanomicins; C080892:pradimicin L; C080896:pradimicin S; C102035:YPD1 protein, S cerevisiae