The Molecular Basis of Catalysis by SDR Family Members Ketoacyl-ACP Reductase FabG and Enoyl-ACP Reductase FabI in Type-II Fatty Acid Biosynthesis
文献类型:期刊论文
作者 | Zhou, Jiashen8; Zhang, Lin8; Wang, Yiran6,7; Song, Wenyan8; Huang, Yuzhou8; Mu, Yajuan8; Schmitz, Werner5; Zhang, Shu-Yu4; Lin, Houwen2,3; Chen, Hong-Zhuan1 |
刊名 | ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
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出版日期 | 2023-10-12 |
页码 | 12 |
关键词 | Acyl-ACP Reductases Allosteric Regulation Biosynthesis Enantioselective Reduction Enzyme Catalysis |
ISSN号 | 1433-7851 |
DOI | 10.1002/anie.202313109 |
通讯作者 | Zhang, Liang(liangzhang2014@sjtu.edu.cn) |
英文摘要 | The short-chain dehydrogenase/reductase (SDR) superfamily members acyl-ACP reductases FabG and FabI are indispensable core enzymatic modules and catalytic orientation controllers in type-II fatty acid biosynthesis. Herein, we report their distinct substrate allosteric recognition and enantioselective reduction mechanisms. FabG achieves allosteric regulation of ACP and NADPH through ACP binding across two adjacent FabG monomers, while FabI follows an irreversible compulsory order of substrate binding in that NADH binding must precede that of ACP on a discrete FabI monomer. Moreover, FabG and FabI utilize a backdoor residue Phe187 or a "rheostat" alpha 8 helix for acyl chain length selection, and their corresponding triad residues Ser142 or Tyr145 recognize the keto- or enoyl-acyl substrates, respectively, facilitating initiation of nucleophilic attack by NAD(P)H. The other two triad residues (Tyr and Lys) mediate subsequent proton transfer and (R)-3-hydroxyacyl- or saturated acyl-ACP production. The distinct substrate allosteric recognition and reduction catalytic mechanisms of ketoacyl-ACP reductase FabG and enoyl-ACP reductase FabI in Type-II fatty acid biosynthesis are reported. The enzymes use alternative catalytic tunnels and core catalytic triads to recognize different ACP, NAD(P)H and fatty acid substrates for asymmetric reduction catalysis.+image |
WOS关键词 | ACYL CARRIER PROTEIN ; CRYSTAL-STRUCTURE ; ESCHERICHIA-COLI ; 6-DEOXYERYTHRONOLIDE B ; SYNTHASE ; MECHANISM ; RESIDUES ; COMPLEX ; INHIBITION ; COFACTOR |
资助项目 | This project was supported by the grants from the National Key Research and Development Program of China (No. 2022YFC2804100 to Liang Zhang), the National Natural Science Foundation of China (Nos. 22077081 to Liang Zhang; 22107067 to Lin Zhang), the Major[2022YFC2804100] ; National Key Research and Development Program of China[91853118] ; National Natural Science Foundation of China[20S11900300] ; National Natural Science Foundation of China[22S11900600] ; Science and Technology Commission of Shanghai Municipality ; Shanghai Education Development Foundation[20SG16] ; Shanghai Municipal Education Commission[SHSMU-ZDCX20212702] ; Innovative Research Team of High-Level Local Universities in Shanghai ; Shanghai Frontiers Science Center of Cellular Homeostasis and Human Diseases |
WOS研究方向 | Chemistry |
语种 | 英语 |
WOS记录号 | WOS:001079470500001 |
出版者 | WILEY-V C H VERLAG GMBH |
源URL | [http://119.78.100.183/handle/2S10ELR8/307345] ![]() |
专题 | 新药研究国家重点实验室 |
通讯作者 | Zhang, Liang |
作者单位 | 1.Shanghai Univ Tradit Chinese Med, Shuguang Hosp, Inst Interdisciplinary Integrat Biomed Res, Shanghai 201203, Peoples R China 2.Shenzhen Polytech, Inst Marine Biomed, Shenzhen 518055, Peoples R China 3.Shanghai Jiao Tong Univ, Ren Ji Hosp, Res Ctr Marine Drugs, Sch Med,State Key Lab Oncogene & Related Genes,Dep, Shanghai 200127, Peoples R China 4.Shanghai Jiao Tong Univ, Sch Chem & Chem Engn, Shanghai 200240, Peoples R China 5.Univ Wurzburg, Dept Biochem & Mol Biol, D-97074 Wurzburg, Germany 6.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 7.Univ Chinese Acad Sci, Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou 310024, Peoples R China 8.Shanghai Jiao Tong Univ Sch Med, Dept Pharmacol & Chem Biol, State Key Lab Syst Med Canc, Sch Med SJTU SM, Shanghai 200025, Peoples R China |
推荐引用方式 GB/T 7714 | Zhou, Jiashen,Zhang, Lin,Wang, Yiran,et al. The Molecular Basis of Catalysis by SDR Family Members Ketoacyl-ACP Reductase FabG and Enoyl-ACP Reductase FabI in Type-II Fatty Acid Biosynthesis[J]. ANGEWANDTE CHEMIE-INTERNATIONAL EDITION,2023:12. |
APA | Zhou, Jiashen.,Zhang, Lin.,Wang, Yiran.,Song, Wenyan.,Huang, Yuzhou.,...&Zhang, Liang.(2023).The Molecular Basis of Catalysis by SDR Family Members Ketoacyl-ACP Reductase FabG and Enoyl-ACP Reductase FabI in Type-II Fatty Acid Biosynthesis.ANGEWANDTE CHEMIE-INTERNATIONAL EDITION,12. |
MLA | Zhou, Jiashen,et al."The Molecular Basis of Catalysis by SDR Family Members Ketoacyl-ACP Reductase FabG and Enoyl-ACP Reductase FabI in Type-II Fatty Acid Biosynthesis".ANGEWANDTE CHEMIE-INTERNATIONAL EDITION (2023):12. |
入库方式: OAI收割
来源:上海药物研究所
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