Enzymes of the mevalonate pathway of isoprenoid biosynthesis.
Enzymes of the mevalonate pathway of isoprenoid biosynthesis.
复制标题
DOI：
10.1016/j.abb.2010.09.028
复制
发表时间：
2011-01-15
影响因子：
3.9
通讯作者：
Miziorko HM
中科院分区：
文献类型：
--
作者：
Miziorko HM
甲羟戊酸途径解释了乙酰辅酶A向异戊烯基5-二磷酸的转化，异戊烯基5-二磷酸是聚类异戊二烯代谢物和天然产物的多功能前体。该途径在大多数真核生物、古细菌和一些真细菌中起作用。直到最近才报道了这种代谢的功能和结构基础。生物合成的乙酰乙酰-CoA硫解酶和HMG-CoA合酶反应依赖于不同但位于在整个初始缩合酶家族中相似的活性位点的关键氨基酸。细菌和动物HMG-CoA还原酶已被广泛研究，这些蛋白质之间的对比和他们的相互作用与他汀类抑制剂的定义。甲羟戊酸转化为异戊烯基5-二磷酸涉及三个ATP依赖性磷酸化反应。虽然负责这三种反应的细菌酶共享一个共同的蛋白质折叠，但动物酶在这方面有所不同，正如最近报道的人磷酸甲羟戊酸激酶的结构所证明的那样。在细菌和动物中对甲羟戊酸磷酸化的代谢物抑制的观察结果之间存在显著的对比。这些反差的结构基础最近也有报道。磷酸甲羟戊酸激酶和甲羟戊酸二磷酸脱羧酶反应的替代物可能存在于古细菌中。因此，关于从乙酰辅酶A合成异戊烯基二磷酸的新细节继续出现。
The mevalonate pathway accounts for conversion of acetyl-CoA to isopentenyl 5-diphosphate, the versatile precursor of polyisoprenoid metabolites and natural products. The pathway functions in most eukaryotes, archaea, and some eubacteria. Only recently has much of the functional and structural basis for this metabolism been reported. The biosynthetic acetoacetyl-CoA thiolase and HMG-CoA synthase reactions rely on key amino acids that are different but are situated in active sites that are similar throughout the family of initial condensation enzymes. Both bacterial and animal HMG-CoA reductases have been extensively studied and the contrasts between these proteins and their interactions with statin inhibitors defined. The conversion of mevalonic acid to isopentenyl 5-diphosphate involves three ATP-dependent phosphorylation reactions. While bacterial enzymes responsible for these three reactions share a common protein fold, animal enzymes differ in this respect as the recently reported structure of human phosphomevalonate kinase demonstrates. There are significant contrasts between observations on metabolite inhibition of mevalonate phosphorylation in bacteria and animals. The structural basis for these contrasts has also recently been reported. Alternatives to the phosphomevalonate kinase and mevalonate diphosphate decarboxylase reactions may exist in archaea. Thus, new details regarding isopentenyl diphosphate synthesis from acetyl-CoA continue to emerge.
登录
查看更多内容
DOI：
10.1016/0167-4838(87)90170-1
发表时间：
1987-12-18
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
CHIEW, YE;OSULLIVAN, WJ;LEE, CS
通讯作者：
LEE, CS
影响因子：
8
作者：
Anstrom, DM;Kallio, K;Remington, SJ
通讯作者：
Remington, SJ
影响因子：
2.9
作者：
Andreassi, John L., II;Vetting, Matthew W.;Bilder, Patrick W.;Roderick, Steven L.;Leyh, Thomas S.
通讯作者：
Leyh, Thomas S.
影响因子：
4
作者：
Dellas, Nikki;Noel, Joseph P.
通讯作者：
Noel, Joseph P.
影响因子：
2.9
作者：
Andreassi, JL;Dabovic, K;Leyh, TS
通讯作者：
Leyh, TS