Ring Contraction Catalyzed by the Metal-Dependent Radical SAM Enzyme: 7-Carboxy-7-deazaguanine Synthase from B. multivorans. Theoretical Insights into the Reaction Mechanism and the Influence of Metal Ions

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	Ring Contraction Catalyzed by the Metal-Dependent Radical SAM Enzyme: 7-Carboxy-7-deazaguanine Synthase from B. multivorans. Theoretical Insights into the Reaction Mechanism and the Influence of Metal Ions
	Zhu, Wenyou ; Liu, Yongjun
	2015-07-01
发表期刊	ACS CATALYSIS
摘要	7-Carboxy-7-deazaguanine synthase (QueE) is a radical S-adenosylmethionine (SAM) enzyme that catalyzes the conversion of 6-carboxy-5,6,7,8-tetrahydropterin (CPH4) to 7-carboxy-7-deazaguanine (CDG). QueE also shows a clear dependence on Mg2+ ion and is considered a new feature for a radical SAM enzyme. The catalytic mechanism of QueE from B. multivorans has been studied using a combined quantum mechanics and molecular mechanics (QM/MM) method. The results of our calculations reveal that the key ring-contraction step involves a bridged intermediate rather than a ring-opening one. For the QueE-Mg2+ system, the elimination of ammonia is calculated to be rate limiting with a free energy barrier of 18.8 kcal/mol, which is basically in accordance with the estimated value (20.9 kcal/mol) from the experiment. For QueE-Na+ complex, the rate-limiting step switches to the formation of the bridged intermediate with an energy barrier of 29.3 kcal/mol. Natural population analysis indicates that the metal ions do not act as Lewis acids; therefore, they mainly play a role in fixing the substrate in its reactive conformation. The different coordination of Mg2+ and Na+ with the substrate is suggested to be the main reason for leading to the different activities of QueE-Mg2+ and QueE-Na+ complexes.; 7-Carboxy-7-deazaguanine synthase (QueE) is a radical S-adenosylmethionine (SAM) enzyme that catalyzes the conversion of 6-carboxy-5,6,7,8-tetrahydropterin (CPH4) to 7-carboxy-7-deazaguanine (CDG). QueE also shows a clear dependence on Mg2+ ion and is considered a new feature for a radical SAM enzyme. The catalytic mechanism of QueE from B. multivorans has been studied using a combined quantum mechanics and molecular mechanics (QM/MM) method. The results of our calculations reveal that the key ring-contraction step involves a bridged intermediate rather than a ring-opening one. For the QueE-Mg2+ system, the elimination of ammonia is calculated to be rate limiting with a free energy barrier of 18.8 kcal/mol, which is basically in accordance with the estimated value (20.9 kcal/mol) from the experiment. For QueE-Na+ complex, the rate-limiting step switches to the formation of the bridged intermediate with an energy barrier of 29.3 kcal/mol. Natural population analysis indicates that the metal ions do not act as Lewis acids; therefore, they mainly play a role in fixing the substrate in its reactive conformation. The different coordination of Mg2+ and Na+ with the substrate is suggested to be the main reason for leading to the different activities of QueE-Mg2+ and QueE-Na+ complexes.
文献类型	期刊论文
条目标识符	http://210.75.249.4/handle/363003/17321
专题	中国科学院西北高原生物研究所
推荐引用方式 GB/T 7714	Zhu, Wenyou,Liu, Yongjun. Ring Contraction Catalyzed by the Metal-Dependent Radical SAM Enzyme: 7-Carboxy-7-deazaguanine Synthase from B. multivorans. Theoretical Insights into the Reaction Mechanism and the Influence of Metal Ions[J]. ACS CATALYSIS,2015.
APA	Zhu, Wenyou,&Liu, Yongjun.(2015).Ring Contraction Catalyzed by the Metal-Dependent Radical SAM Enzyme: 7-Carboxy-7-deazaguanine Synthase from B. multivorans. Theoretical Insights into the Reaction Mechanism and the Influence of Metal Ions.ACS CATALYSIS.
MLA	Zhu, Wenyou,et al."Ring Contraction Catalyzed by the Metal-Dependent Radical SAM Enzyme: 7-Carboxy-7-deazaguanine Synthase from B. multivorans. Theoretical Insights into the Reaction Mechanism and the Influence of Metal Ions".ACS CATALYSIS (2015).