Acetyl coenzyme A synthesis from unnatural methylated corrinoids: requirement for "base-off" coordination at cobalt.
Acetyl coenzyme A synthesis from unnatural methylated corrinoids: requirement for "base-off" coordination at cobalt.
复制标题
非天然甲基化咕啉的乙酰辅酶 A 合成：钴“碱基关闭”配位的要求。
DOI：
10.1021/ja005709k
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发表时间：
2001
影响因子：
15
通讯作者：
Ragsdale,SW
中科院分区：
文献类型：
--
作者：
Seravalli,J;Brown,KL;Ragsdale,SW
该通讯报道，甲基钴酰胺1（MeCbi），它缺乏一个较低的轴向氮供体配体钴，是乙酰辅酶A合成的镍铁硫酶，乙酰辅酶A合成酶（ACS）的底物。相比之下，含有二甲基苯并咪唑配体的甲钴胺（MeCbl）的反应性比MeCbi或其中配位氮被甲基化且不能结合钴的MeCbl类似物低2000倍。此外，CO脱氢酶（CODH）催化Cbi的CO依赖性还原的速率比Cbl快约10 000倍。这些结果支持的假设，缺乏一个较低的轴向氮供体配体钴在天然corrinoid铁硫蛋白（CFeSP）产甲烷和产乙酸微生物增强其还原活化和脱甲基反应的倾向。CODH/ACS双功能酶是Wood-Ljungdahl自养CO2固定途径的核心。2，3CODH催化CO2的双电子还原为CO（等式1），ACS催化从CO（甲基供体）和CoA合成乙酰辅酶A（等式2）。等式2中的中间步骤是将钴结合的甲基从甲基化CFeSP（Me-CFeSP）转移到ACS（等式3）。这似乎是ACS的亲核中心的SN 2攻击，推测是Ni，4对CFeSP的甲基-Co（III）状态的攻击，产生Co（I）5，6并甲基化ACS。生理甲基供体是甲基化的CFeSP。七、八
This communication reports that methylcobinamide1 (MeCbi), which lacks a lower axial nitrogen donor ligand to cobalt, is a substrate for acetyl-CoA synthesis by the nickel iron-sulfur enzyme, acetyl-CoA synthase (ACS). In contrast, methylcobalamin (MeCbl), which contains a dimethylbenzimidazole ligand, is 2000-fold less reactive than MeCbi or a MeCbl analogue in which the coordinating nitrogen is methylated and cannot bind cobalt. Furthermore, CO dehydrogenase (CODH) catalyzes the CO-dependent reduction of Cbi at a rate approximately 10 000-fold faster than that of Cbl. These results support the hypothesis that lack of a lower axial nitrogen donor ligand to cobalt in the native corrinoid iron-sulfur protein (CFeSP) from methanogenic and acetogenic microbes enhances its propensity for reductive activation and demethylation reactions. The bifunctional enzyme, CODH/ACS, is central to the Wood-Ljungdahl pathway of autotrophic CO2 fixation. 2, 3 CODH catalyzes the two-electron reduction of CO2 to CO (eq 1), and ACS catalyzes acetyl-CoA synthesis from CO, the methyl-donor, and CoA (eq 2). An intermediate step in eq 2 is transfer of the cobaltbound methyl group from the methylated CFeSP (Me-CFeSP) to ACS (eq 3). This appears to be an SN2 attack of a nucleophilic center of ACS, presumably Ni, 4 on the methyl-Co (III) state of the CFeSP, generating Co (I) 5, 6 and methylating ACS. The physiological methyl donor is the methylated CFeSP. 7, 8