Organometallic Complex Formed by an Unconventional Radical S-Adenosylmethionine Enzyme

被引:17
|
作者
Dong, Min [1 ]
Horitani, Masaki [2 ]
Dzikovski, Boris [1 ]
Pandelia, Maria-Eirini [3 ]
Krebs, Carsten [4 ,5 ]
Freed, Jack H. [1 ]
Hoffman, Brian M. [2 ]
Lin, Hening [1 ,6 ]
机构
[1] Cornell Univ, Dept Chem & Chem Biol, Ithaca, NY 14853 USA
[2] Northwestern Univ, Dept Chem, Evanston, IL 60208 USA
[3] Brandeis Univ, Dept Biochem, Waltham, MA 02453 USA
[4] Penn State Univ, Dept Chem, University Pk, PA 16802 USA
[5] Penn State Univ, Dept Biochem & Mol Biol, University Pk, PA 16802 USA
[6] Cornell Univ, Howard Hughes Med Inst, Ithaca, NY 14853 USA
关键词
BIOSYNTHESIS; MECHANISM; INTERMEDIATE; INHIBITION; CATALYSIS;
D O I
10.1021/jacs.6b04155
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Pyrococcus horikoshii Dph2 (PhDph2) is an unusual radical S-adenosylmethionine (SAM) enzyme involved in the first step of diphthamide biosynthesis. It catalyzes the reaction by cleaving SAM to generate a 3-amino-3-carboxypropyl (ACP) radical. To probe the reaction mechanism, we synthesized a SAM analogue (SAMcA), in which the ACP group of SAM is replaced with a 3-carboxyally1 group. SAMcA. is cleaved by PhDph2, yielding a paramagnetic (S = 1/2) species, which is assigned to a complex formed between the reaction product, alpha-sulfinyl-3-butenoic acid, and the [4Fe-4S] cluster. Electron nuclear double resonance (ENDOR) measurements with C-13 and H-2 isotopically labeled SAM(CA) support a sr-complex between the C=C double bond of asulfinyl-3-butenoic acid and the unique iron of the [4Fe-4S] cluster. This is the first example of a radical SAM-related [4Fe-4S](+) cluster forming an organometallic complex with an alkene, shedding additional light on the mechanism of PhDph2 and expanding our current notions for the reactivity of [4Fe-4S] clusters in radical SAM enzymes.
引用
收藏
页码:9755 / 9758
页数:4
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