Leaver M J, George S G
Institute of Aquaculture, University of Stirling, FK9 4LA, Stirling, UK.
Gene. 2000 Oct 3;256(1-2):83-91. doi: 10.1016/s0378-1119(00)00373-5.
Tetrapod cytochrome P4501 family (CYP1A1, CYP1A2 and CYP1B1) enzymes are most active in hydroxylating a variety of environmental contaminants including polyaromatic hydrocarbons (PAH), planar polychlorinated biphenyls and arylamines and thus play a pivotal role in the toxicology of these compounds. Mammalian CYP1A1 and CYP1A2 genes appear to have diverged after the evolutionary emergence of mammals, whereas fish species apparently possess only one CYP1A family gene, and fish CYP1A enzymes exhibit properties of both of the mammalian isoforms. We have isolated a further CYP1 family gene from a marine flatfish (plaice; Pleuronectes platessa), which, on the basis of exon organisation and sequence similarity, can be assigned as a piscine CYP1B. Its deduced amino acid sequence shows the closest (54%) identity to mammalian CYP1B1 proteins and, on the basis of molecular modeling studies, shows a high degree of positional and structural conservation of the substrate contacting amino acid residues in its putative active site when compared to other CYP1 enzymes. Phylogenetic analysis of fish and mammalian CYP1 family sequences indicates that the plaice CYP1B and mammalian CYP1B1 genes share a common ancestry. Plaice CYP1B has a more restricted tissue expression profile than the previously isolated plaice CYP1A, only being detectable, by Northern blotting, in gill tissue. In contrast to CYP1A, which shows extensive PAH-dependent induction in a variety of tissues, plaice CYP1B appears unresponsive to treatment with a prototypical PAH-type inducer, beta-naphthoflavone (BNF).
四足动物细胞色素P4501家族（CYP1A1、CYP1A2和CYP1B1）酶在羟基化多种环境污染物（包括多环芳烃（PAH）、平面多氯联苯和芳基胺）方面活性最高，因此在这些化合物的毒理学中起关键作用。哺乳动物的CYP1A1和CYP1A2基因似乎在哺乳动物进化出现后发生了分化，而鱼类显然只拥有一个CYP1A家族基因，并且鱼类CYP1A酶表现出两种哺乳动物同工型的特性。我们从一种海产比目鱼（鲽鱼；欧洲鲽）中分离出了另一个CYP1家族基因，根据外显子组织和序列相似性，它可被归类为鱼类CYP1B。其推导的氨基酸序列与哺乳动物CYP1B1蛋白的相似度最高（54%），并且基于分子建模研究，与其他CYP1酶相比，其假定活性位点中与底物接触的氨基酸残基在位置和结构上具有高度保守性。对鱼类和哺乳动物CYP1家族序列的系统发育分析表明，鲽鱼CYP1B和哺乳动物CYP1B1基因有共同的祖先。鲽鱼CYP1B的组织表达谱比先前分离出的鲽鱼CYP1A更受限，通过Northern印迹法仅在鳃组织中可检测到。与在多种组织中表现出广泛的PAH依赖性诱导的CYP1A不同，鲽鱼CYP1B似乎对典型的PAH型诱导剂β-萘黄酮（BNF）处理无反应。
