期刊
CELLULAR AND MOLECULAR LIFE SCIENCES
卷 70, 期 10, 页码 1807-1830出版社
SPRINGER BASEL AG
DOI: 10.1007/s00018-012-1229-5
关键词
Aldehyde oxidase; Molybdo-flavoenzyme; Drug metabolism; Molybdenum cofactor
资金
- Telethon-Italy Foundation
- Fondazione Cariplo
- Fondazione Italo Monzino
- Negri-Weizmann Foundation
- Associazione Italiana per la Ricerca contro il Cancro (AIRC)
Aldehyde oxidases (AOXs) and xanthine dehydrogenases (XDHs) belong to the family of molybdo-flavoenzymes. Although AOXs are not identifiable in fungi, these enzymes are represented in certain protists and the majority of plants and vertebrates. The physiological functions and substrates of AOXs are unknown. Nevertheless, AOXs are major drug metabolizing enzymes, oxidizing a wide range of aromatic aldehydes and heterocyclic compounds of medical/toxicological importance. Using genome sequencing data, we predict the structures of AOX genes and pseudogenes, reconstructing their evolution. Fishes are the most primitive organisms with an AOX gene (AOX alpha), originating from the duplication of an ancestral XDH. Further evolution of fishes resulted in the duplication of AOX alpha into AOX beta and successive pseudogenization of AOX alpha. AOX beta is maintained in amphibians and it is the likely precursors of reptilian, avian, and mammalian AOX1. Amphibian AOX gamma is a duplication of AOX beta and the likely ancestor of reptilian and avian AOX2, which, in turn, gave rise to mammalian AOX3L1. Subsequent gene duplications generated the two mammalian genes, AOX3 and AOX4. The evolution of mammalian AOX genes is dominated by pseudogenization and deletion events. Our analysis is relevant from a structural point of view, as it provides information on the residues characterizing the three domains of each mammalian AOX isoenzyme. We cloned the cDNAs encoding the AOX proteins of guinea pig and cynomolgus monkeys, two unique species as to the evolution of this enzyme family. We identify chimeric RNAs from the human AOX3 and AOX3L1 pseudogenes with potential to encode a novel microRNA.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据