2‐Oxo Acid Dehydrogenase Multienzyme Complexes: Domains, Dynamics, and Design a
2‐Oxo Acid Dehydrogenase Multienzyme Complexes: Domains, Dynamics, and Design a
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2-含氧酸脱氢酶多酶复合物：结构域、动力学和设计
DOI：
--
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发表时间：
1989
影响因子：
5.2
通讯作者：
L. Packman
中科院分区：
文献类型：
--
作者：
R. Perham;L. Packman
2-0x0酸脱氢酶多酶复合体催化2-0x0酸氧化脱羧基，释放CoZ，生成相应的酰基辅酶A。已知有三个主要系统：它们各自的底物是丙酮酸、2-氧戊二酸和支链2-0x0酸，它们分别通过转氨基作用转化为缬氨酸、亮氨酸和异亮氨酸(有关它们的结构、机制和遗传学的最新综述，请参阅参考文献)。1和2)。丙酮酸脱氢酶(PDH)复合体的组成酶是丙酮酸脱羧酶(丙酮酸脱氢酶[硫辛酰胺]，ELP：EC 1.2.4.1)、二氢硫胺乙酰转移酶(E2P：EC 2.3.1.12)和二氢硫辛酰胺脱氢酶(E3：EC 1.8.1.4)。2-氧戊二酸脱氢酶复合体的相应酶是2-氧戊二酸脱羧酶(ELO：EC 1.2.4.2)、二氢硫胺琥珀酰基转移酶(E20：EC 2.3.1.61)和二氢硫胺脱氢酶(E3：EC 1.8.1.4)。类似的酶构成支链2-0x0酸脱氢酶~o m p L e x。在催化过程中，底物以硫酯键连接到硫酰-赖氨酸残基(图2)。I)，这基本上形成了自由旋转的摆动手臂。硫辛基赖氨酸残基本身存在于小的硫辛基结构域中，这些结构域位于E2多肽链的氨基末端。E2链的羧基末端部分包括至少两个已知功能的折叠结构域：它们体现了酰基转移酶活性，催化酰基从硫辛基赖氨酸残基转移到辅酶A，它们以八面体(24-聚体)或二十面体(60-聚体)对称聚集，提供了E-L和E3亚基组装所围绕的内部结构核心。正如在其他地方所回顾的，‘硫辛基结构域可以相对于2-0x0酸脱氢酶复合体的大部分移动，这是由于在E2链的结构域间发现的构象灵活性，并且这种移动是催化性能的重要贡献。因此，E2链特别令人感兴趣，因为它们提供了酶复合体的中心结构和机械核心。在这篇文章中，我们进一步综述了我们对E2链的结构域结构、多肽链的结构域间段的动力学以及这些
The 2-0x0 acid dehydrogenase multienzyme complexes catalyze the oxidative decarboxylation of 2-0x0 acids, releasing COz and generating the relevant acylCoA. Three principal systems are known; these have as their respective substrates pyruvate, 2-oxoglutarate, and the branched-chain 2-0x0 acids related by transamination to valine, leucine, and isoleucine, respectively (for recent reviews of their structure, mechanism and genetics, see Refs. 1 and 2). The reaction catalyzed' is shown in schematic form in FIGURE 1. The constituent enzymes of the pyruvate dehydrogenase (PDH) complex are pyruvate decarboxylase (pyruvate dehydrogenase [lipoamide], Elp: EC 1.2.4.1), dihydrolipoamide acetyltransferase (E2p: E C 2.3.1.12), and dihydrolipoamide dehydrogenase (E3: E C 1.8.1.4). The corresponding enzymes of the 2-oxoglutarate dehydrogenase (20GDH) complex are 2-oxoglutarate decarboxylase (Elo: EC 1.2.4.2), dihydrolipoamide succinyltransferase (E20: EC 2.3.1.61), and dihydrolipoamide dehydrogenase (E3: E C 1.8.1.4). Similar enzymes constitute the branched-chain 2-0x0 acid dehydrogenase ~ o m p l e x . ~ During catalysis, the substrate is attached in thioester linkage to lipoyl-lysine residues (FIG. I ) , which form essentially freely rotating swinging arms. The lipoyllysine residues are themselves housed in small lipoyl domains which are located in the amino-terminal portions of the E2 polypeptide chains. The carboxyl-terminal portions of the E2 chains comprise larger folded domains that serve at least two known functions: they embody the acyltransferase activity that catalyzes the transfer of the acyl group from the lipoyl-lysine residue to coenzyme A and they aggregate with octahedral (24-mer) or icosahedral(60-mer) symmetry to provide the inner structural core around which the E l and E3 subunits are assembled. As reviewed elsewhere,' the lipoyl domains can move with respect to the bulk of a 2-0x0 acid dehydrogenase complex by virtue of the conformational flexibility found in the interdomain segments of the E2 chains, and this movement is an important contributor to the catalytic properties. Thus, the E2 chains are of particular interest in that they provide the central structural and mechanistic cores of the enzyme complexes. In this article, we review further recent advances in our understanding of the domain structure of the E2 chains, the dynamics of the interdomain segments of polypeptide chain, and the way these
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大肠杆菌丙酮酸脱氢酶多酶复合物活性位点耦合机制的计算机模型分析。
DOI：
10.1073/pnas.80.10.2907
发表时间：
1983
影响因子：
11.1
作者：
Hackert,ML;Oliver,RM;Reed,LJ
通讯作者：
Reed,LJ
兔肝支链α-酮酸脱氢酶的分离和磷酸化调节。
DOI：
--
发表时间：
1982
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Paxton,R;Harris,RA
通讯作者：
Harris,RA
使用胰蛋白酶和脂酰胺酶研究硫辛酸部分在大肠杆菌的丙酮酸和 α-酮戊二酸脱氢酶复合物中的作用。
影响因子：
2.9
作者：
Stepp,LR;Bleile,DM;McRorie,DK;Pettit,FH;Reed,LJ
通讯作者：
Reed,LJ
牛心丙酮酸脱氢酶复合物二氢硫辛酰转乙酰酶成分的亚基结构。
DOI：
--
发表时间：
1981
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Bleile,DM;Hackert,ML;Pettit,FH;Reed,LJ
通讯作者：
Reed,LJ
铜绿假单胞菌 PAO 支链含氧酸脱氢酶复合物的分离。
DOI：
10.1042/bj2330737
发表时间：
1986
期刊：
The Biochemical journal
影响因子：
--
作者：
McCully,V;Burns,G;Sokatch,JR
通讯作者：
Sokatch,JR