来自克鲁维酵母的两种不同的二氢乳清酸脱氢酶。
Two different dihydroorotate dehydrogenases from yeast Saccharomyces kluyveri.
作者信息
Zameitat Elke, Knecht Wolfgang, Piskur Jure, Löffler Monika
机构信息
Institute for Physiological Chemistry, Philipps-University, Karl-von-Frisch-Strasse 1, D-35033 Marburg, Germany.
出版信息
FEBS Lett. 2004 Jun 18;568(1-3):129-34. doi: 10.1016/j.febslet.2004.05.017.
Genes for two structurally and functionally different dihydroorotate dehydrogenases (DHODHs, EC 1.3.99.11), catalyzing the fourth step of pyrimidine biosynthesis, have been previously found in yeast Saccharomyces kluyveri. One is closely related to the Schizosaccharomyces pombe mitochondrial family 2 enzymes, which use quinones as direct and oxygen as the final electron acceptor. The other one resembles the Saccharomyces cerevisiae cytosolic family 1A fumarate-utilizing DHODH. The DHODHs from S. kluyveri, Sch. pombe and S. cerevisiae, were expressed in Escherichia coli and compared for their biochemical properties and interaction with inhibitors. Benzoates as pyrimidine ring analogs were shown to be selective inhibitors of cytosolic DHODs. This unique property of Saccharomyces DHODHs could appoint DHODH as a species-specific target for novel anti-fungal therapeutics.
先前已在克鲁维酵母（Saccharomyces kluyveri）中发现了两种结构和功能不同的二氢乳清酸脱氢酶（DHODHs，EC 1.3.99.11）的基因，它们催化嘧啶生物合成的第四步。其中一种与粟酒裂殖酵母（Schizosaccharomyces pombe）线粒体家族2酶密切相关，该酶使用醌作为直接电子受体，氧气作为最终电子受体。另一种类似于酿酒酵母（Saccharomyces cerevisiae）胞质家族1A利用富马酸的DHODH。将来自克鲁维酵母、粟酒裂殖酵母和酿酒酵母的DHODHs在大肠杆菌中表达，并比较它们的生化特性以及与抑制剂的相互作用。已证明苯甲酸酯作为嘧啶环类似物是胞质DHODs的选择性抑制剂。酿酒酵母DHODHs的这种独特特性可能使DHODH成为新型抗真菌治疗药物的物种特异性靶点。
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