Knowledge Management System of Northwest Institute of Plateau Biology, CAS
| Theoretical Study of the Catalytic Mechanism of E1 Subunit of Pyruvate Dehydrogenase Multienzyme Complex from Bacillus stearothermophilus | |
| Sheng, Xiang1; Liu, Yongjun1,2; Liu, YJ (reprint author), Shandong Univ, Sch Chem & Chem Engn, Key Lab Theoret & Computat Chem, Jinan 250100, Shandong, Peoples R China. | |
| 2013-11-12 | |
| 发表期刊 | BIOCHEMISTRY
 |
| ISSN | 0006-2960 |
| 卷号 | 52期号:45页码:8079-8093 |
| 文章类型 | Article |
| 摘要 | Pyruvate dehydrogenase multienzyme complex (PDHc) is a member of a family of 2-oxo acid dehydrogenase (OADH) multienzyme complexes involved in several central points of oxidative metabolism, and the E1 subunit is the most important component in the entire PDHc catalytic system, which catalyzes the reversible transfer of an acetyl group from a pyruvate to the lipoyl group of E2 subunit lipoly domain. In this article, the catalytic mechanism of the E1 subunit has been systematically studied using density functional theory (DFT). Four possible pathways with different general acid/base catalysts in decarboxylation and reductive acylation processes were explored. Our calculation results indicate that the 4'-amino pyrimidine of ThDP and residue His128 are the most likely proton donors in the decarboxylation and reductive acylation processes, respectively. During the reaction, each C-C and C-S bond formation or cleavage process, except for the liberation of CO2, is always accompanied by a proton transfer between the substrates and proton donors. The liberation of CO2 is calculated to be the rate-limiting step for the overall reaction, with an energy barrier of 13.57 kcal/mol. The decarboxylation process is endothermic by 5.32 kcal/mol, whereas the reductive acylation process is exothermic with a value of 5.74 kcal/mol. The assignment of protonation states of the surrounding residues can greatly influence the reaction. Residues His128 and His271 play roles in positioning the first substrate pyruvate and second substrate lipoyl group, respectively.; Pyruvate dehydrogenase multienzyme complex (PDHc) is a member of a family of 2-oxo acid dehydrogenase (OADH) multienzyme complexes involved in several central points of oxidative metabolism, and the E1 subunit is the most important component in the entire PDHc catalytic system, which catalyzes the reversible transfer of an acetyl group from a pyruvate to the lipoyl group of E2 subunit lipoly domain. In this article, the catalytic mechanism of the E1 subunit has been systematically studied using density functional theory (DFT). Four possible pathways with different general acid/base catalysts in decarboxylation and reductive acylation processes were explored. Our calculation results indicate that the 4'-amino pyrimidine of ThDP and residue His128 are the most likely proton donors in the decarboxylation and reductive acylation processes, respectively. During the reaction, each C-C and C-S bond formation or cleavage process, except for the liberation of CO2, is always accompanied by a proton transfer between the substrates and proton donors. The liberation of CO2 is calculated to be the rate-limiting step for the overall reaction, with an energy barrier of 13.57 kcal/mol. The decarboxylation process is endothermic by 5.32 kcal/mol, whereas the reductive acylation process is exothermic with a value of 5.74 kcal/mol. The assignment of protonation states of the surrounding residues can greatly influence the reaction. Residues His128 and His271 play roles in positioning the first substrate pyruvate and second substrate lipoyl group, respectively. |
| WOS标题词 | Science & Technology ; Life Sciences & Biomedicine |
| DOI | 10.1021/bi400577f |
| 关键词[WOS] | THIAMIN DIPHOSPHATE ; ESCHERICHIA-COLI ; ACTIVE-SITES ; ACETOHYDROXYACID SYNTHASE ; PSEUDOMONAS-AERUGINOSA ; LIPOYL DOMAIN ; ENZYMES ; DEFICIENCY ; COMPONENT ; TRANSKETOLASE |
| 收录类别 | SCI |
| 语种 | 英语 |
| 项目资助者 | Natural Science Foundation of China(21373125 ; 21173129) |
| WOS研究方向 | Biochemistry & Molecular Biology |
| WOS类目 | Biochemistry & Molecular Biology |
| WOS记录号 | WOS:000330017700020 |
| 引用统计 | |
| 文献类型 | 期刊论文 |
| 条目标识符 | http://210.75.249.4/handle/363003/3899 |
| 专题 | 中国科学院西北高原生物研究所 |
| 通讯作者 | Liu, YJ (reprint author), Shandong Univ, Sch Chem & Chem Engn, Key Lab Theoret & Computat Chem, Jinan 250100, Shandong, Peoples R China. |
| 作者单位 | 1.Shandong Univ, Sch Chem & Chem Engn, Key Lab Theoret & Computat Chem, Jinan 250100, Shandong, Peoples R China 2.Chinese Acad Sci, Northwest Inst Plateau Biol, Xining 810001, Qinghai, Peoples R China |
| 推荐引用方式 GB/T 7714 | Sheng, Xiang,Liu, Yongjun,Liu, YJ . Theoretical Study of the Catalytic Mechanism of E1 Subunit of Pyruvate Dehydrogenase Multienzyme Complex from Bacillus stearothermophilus[J]. BIOCHEMISTRY,2013,52(45):8079-8093. |
| APA | Sheng, Xiang,Liu, Yongjun,&Liu, YJ .(2013).Theoretical Study of the Catalytic Mechanism of E1 Subunit of Pyruvate Dehydrogenase Multienzyme Complex from Bacillus stearothermophilus.BIOCHEMISTRY,52(45),8079-8093. |
| MLA | Sheng, Xiang,et al."Theoretical Study of the Catalytic Mechanism of E1 Subunit of Pyruvate Dehydrogenase Multienzyme Complex from Bacillus stearothermophilus".BIOCHEMISTRY 52.45(2013):8079-8093. |
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