Structural basis for different specificities of acyltransferases associated with the human cytosolic and mitochondrial fatty acid synthases.
Structural basis for different specificities of acyltransferases associated with the human cytosolic and mitochondrial fatty acid synthases.
复制标题
DOI：
10.1016/j.chembiol.2009.04.011
复制
发表时间：
2009-06-26
影响因子：
--
通讯作者：
Smith S
中科院分区：
文献类型：
--
作者：
Bunkoczi G;Misquitta S;Wu X;Lee WH;Rojkova A;Kochan G;Kavanagh KL;Oppermann U;Smith S
动物使用两个系统进行脂肪酸的从头合成：胞浆中的超级合成酶复合体(类型I)主要产生棕榈酸，线粒体中的独立酶(类型II)主要产生辛酰基部分。在这两个区段中负责启动脂肪酸生物合成的酰基转移酶因其不同的底物特异性而有所区别：I型酶既转移乙酰基底物又转移丙二酰基扩链剂，而II型酶只负责丙二酰基底物的转移。第一类和第二类酶的晶体结构，在电子底物对接研究和改变其各自特异性的诱变实验的支持下，揭示了尽管这两种酶采用了相似的整体折叠，但其催化中心的细微差异导致了它们不同的特异性。
Animals employ two systems for the de novo biosynthesis of fatty acids: a megasynthase complex in the cytosol (type I) that produces mainly palmitate, and an ensemble of freestanding enzymes in the mitochondria (type II) that produces mainly octanoyl moieties. The acyltransferases responsible for initiation of fatty acid biosynthesis in the two compartments are distinguished by their different substrate specificities: the type I enzyme transfers both the acetyl primer and the malonyl chain extender, whereas the type II enzyme is responsible for translocation of only the malonyl substrate. Crystal structures for the type I and II enzymes, supported by in silico substrate docking studies and mutagenesis experiments that alter their respective specificities, reveal that although the two enzymes adopt a similar overall fold, subtle differences at their catalytic centers account for their different specificities.
登录
查看更多内容
影响因子：
4.8
作者：
Gueguen, V;Macherel, D;Bourguignon, J
通讯作者：
Bourguignon, J
影响因子：
56.9
作者：
Maier, Timm;Leibundgut, Marc;Ban, Nenad
通讯作者：
Ban, Nenad
影响因子：
3.3
作者：
CLARKE, SD
通讯作者：
CLARKE, SD
影响因子：
5.7
作者：
Keatinge-Clay, AT;Shelat, AA;Stroud, RM
通讯作者：
Stroud, RM
DOI：
10.1073/pnas.0601924103
发表时间：
2006-07-25
影响因子：
11.1
作者：
Tang, Yinyan;Kim, Chu-Young;Khosla, Chaitan
通讯作者：
Khosla, Chaitan