文章基本信息

标题：Precursor of ether phospholipids is synthesized by a flavoenzyme through covalent catalysis
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作者：Simone Nenci ; Valentina Piano ; Sara Rosati 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2012
卷号：109
期号：46
页码：18791-18796
DOI：10.1073/pnas.1215128109
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：The precursor of the essential ether phospholipids is synthesized by a peroxisomal enzyme that uses a flavin cofactor to catalyze a reaction that does not alter the redox state of the substrates. The enzyme crystal structure reveals a V-shaped active site with a narrow constriction in front of the prosthetic group. Mutations causing inborn ether phospholipid deficiency, a very severe genetic disease, target residues that are part of the catalytic center. Biochemical analysis using substrate and flavin analogs, absorbance spectroscopy, mutagenesis, and mass spectrometry provide compelling evidence supporting an unusual mechanism of covalent catalysis. The flavin functions as a chemical trap that promotes exchange of an acyl with an alkyl group, generating the characteristic ether bond. Structural comparisons show that the covalent versus noncovalent mechanistic distinction in flavoenzyme catalysis and evolution relies on subtle factors rather than on gross modifications of the cofactor environment.
关键词：peroxisomal disorder ; phospholipid biosynthesis ; plasmalogen ; rhizomelic chondrodysplasia punctata