Fischer H, Erdmann S, Holler E
Institut für Biophysik und physikalische Biochemie, Universität Regenburg, West Germany.
Biochemistry. 1989 Jun 13;28(12):5219-26. doi: 10.1021/bi00438a045.
From extracts of microplasmodia of Physarum polycephalum and their culture medium, an unusual substance was isolated which inhibited homologous DNA polymerase alpha of this slime mold but not beta-like DNA polymerase and not heterologous DNA polymerases. Analysis, especially NMR spectroscopy, revealed the major component to be an anionic polyester of L-malic acid and the inhibition to be due to poly(L-malate) in binding reversibly to DNA polymerase alpha. The mode of inhibition is competitive with substrate DNA and follows an inhibition constant Ki = 10 ng/mL. Inhibition is reversed in the presence of spermine, spermidine, poly(ethylene imine), and calf thymus histone H1. According to its ester nature, the inhibitor is slightly labile at neutral and instable at acid and alkaline conditions. Its largest size corresponds to a molecular mass of 40-50 kDa, but the bulk of the material after purification has lower molecular masses. The inhibitory activity depends on the polymer size and has a minimal size requirement.
从多头绒泡菌的微质团提取物及其培养基中，分离出一种不寻常的物质，它能抑制这种黏菌的同源DNA聚合酶α，但不抑制β样DNA聚合酶，也不抑制异源DNA聚合酶。分析，尤其是核磁共振光谱分析表明，主要成分是L-苹果酸的阴离子聚酯，抑制作用是由于聚（L-苹果酸）与DNA聚合酶α可逆结合所致。抑制模式与底物DNA竞争，抑制常数Ki = 10 ng/mL。在精胺、亚精胺、聚（乙烯亚胺）和小牛胸腺组蛋白H1存在下，抑制作用可被逆转。根据其酯的性质，该抑制剂在中性条件下略有不稳定，在酸性和碱性条件下不稳定。其最大尺寸对应于40-50 kDa的分子量，但纯化后的大部分物质分子量较低。抑制活性取决于聚合物大小，并且有最小尺寸要求。
