Pendini Nicole R, Bailey Lisa M, Booker Grant W, Wilce Matthew C, Wallace John C, Polyak Steven W
School of Molecular and Biomedical Science, University of Adelaide, North Tce, Adelaide, South Australia 5005, Australia.
Biochim Biophys Acta. 2008 Jul-Aug;1784(7-8):973-82. doi: 10.1016/j.bbapap.2008.03.011. Epub 2008 Apr 9.
The attachment of biotin onto the biotin-dependent enzymes is catalysed by biotin protein ligase (BPL), also known as holocarboxylase synthase HCS in mammals. Mammals contain five biotin-enzymes that participate in a number of important metabolic pathways such as fatty acid biogenesis, gluconeogenesis and amino acid catabolism. All mammalian biotin-enzymes are post-translationally biotinylated, and therefore activated, through the action of a single HCS. Substrate recognition by BPLs occurs through conserved structural cues that govern the specificity of biotinylation. Defects in biotin metabolism, including HCS, give rise to multiple carboxylase deficiency (MCD). Here we review the literature on this important enzyme. In particular, we focus on the new information that has been learned about BPL's from a number of recently published protein structures. Through molecular modelling studies insights into the structural basis of HCS deficiency in MCD are discussed.
生物素与生物素依赖性酶的连接由生物素蛋白连接酶（BPL）催化，在哺乳动物中也称为全羧化酶合成酶HCS。哺乳动物含有五种生物素酶，它们参与许多重要的代谢途径，如脂肪酸生物合成、糖异生和氨基酸分解代谢。所有哺乳动物的生物素酶都是通过单一HCS的作用进行翻译后生物素化，从而被激活。BPL对底物的识别通过控制生物素化特异性的保守结构线索来实现。生物素代谢缺陷，包括HCS缺陷，会导致多种羧化酶缺乏症（MCD）。在此，我们综述关于这种重要酶的文献。特别地，我们关注从最近发表的一些蛋白质结构中获得的关于BPL的新信息。通过分子建模研究，讨论了对MCD中HCS缺乏的结构基础的见解。
