Murakami-Murofushi K, Shioda M, Kaji K, Yoshida S, Murofushi H
Department of Biology, Faculty of Science, Ochanomizu University, Tokyo, Japan.
J Biol Chem. 1992 Oct 25;267(30):21512-7.
A specific inhibitor of DNA polymerase alpha was isolated from the lipid fraction prepared from myxoamoebae of a true slime mold, Physarum polycephalum. The purified substance was subjected to structural studies by fast atom bombardment mass spectroscopy, infrared spectroscopy, and two-dimensional nuclear magnetic resonance spectroscopy. The structure of this substance was thereby suggested to be a novel lysophosphatidic acid (LPA) composed of cyclic phosphate and cyclopropane-containing hexadecanoic acid. Then we named this substance PHYLPA (Physarum LPA). PHYLPA inhibited more than 80% of the affinity-purified calf thymus DNA polymerase alpha activity at a concentration of 10 micrograms/ml (approximately 20 microM). Inhibition was observed for DNA polymerase alpha but not for DNA polymerase beta or gamma from various eukaryotic species, nor did it inhibit DNA polymerase I from E. coli. From kinetic analyses, the inhibition was considered to be caused by the interaction of PHYLPA with the template DNA.
从一种真黏菌多头绒泡菌的黏液变形体制备的脂质部分中分离出了一种DNA聚合酶α的特异性抑制剂。通过快原子轰击质谱、红外光谱和二维核磁共振光谱对纯化后的物质进行了结构研究。由此推测该物质的结构是一种由环磷酸和含环丙烷的十六烷酸组成的新型溶血磷脂酸（LPA）。然后我们将该物质命名为PHYLPA（绒泡菌LPA）。在浓度为10微克/毫升（约20微摩尔）时，PHYLPA抑制了超过80%的亲和纯化小牛胸腺DNA聚合酶α的活性。观察到它对DNA聚合酶α有抑制作用，但对来自各种真核生物的DNA聚合酶β或γ没有抑制作用，对大肠杆菌的DNA聚合酶I也没有抑制作用。通过动力学分析，认为这种抑制是由PHYLPA与模板DNA的相互作用引起的。
