Structural Characterization and Functional Analysis of Mevalonate Kinase from <i>Tribolium castaneum</i> (Red Flour Beetle)
Mevalonate kinase (MevK) is an important enzyme in the mevalonate pathway that catalyzes the phosphorylation of mevalonate into phosphomevalonate and is involved in juvenile hormone biosynthesis. Herein, we present a structure model of MevK from the red flour beetle <i>Tribolium castaneum</...
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2024-02-01
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author | Haogang Zheng Yuanyuan Yang Ying Hu Jiaxuan Shi Qiaohui Li Yuanqiang Wang Qingyou Xia Pengchao Guo |
author_facet | Haogang Zheng Yuanyuan Yang Ying Hu Jiaxuan Shi Qiaohui Li Yuanqiang Wang Qingyou Xia Pengchao Guo |
author_sort | Haogang Zheng |
collection | DOAJ |
description | Mevalonate kinase (MevK) is an important enzyme in the mevalonate pathway that catalyzes the phosphorylation of mevalonate into phosphomevalonate and is involved in juvenile hormone biosynthesis. Herein, we present a structure model of MevK from the red flour beetle <i>Tribolium castaneum</i> (<i>Tc</i>MevK), which adopts a compact α/β conformation that can be divided into two parts: an N-terminal domain and a C-terminal domain. A narrow, deep cavity accommodating the substrate and cofactor was observed at the junction between the two domains of <i>Tc</i>MevK. Computational simulation combined with site-directed mutagenesis and biochemical analyses allowed us to define the binding mode of <i>Tc</i>MevK to cofactors and substrates. Moreover, <i>Tc</i>MevK showed optimal enzyme activity at pH 8.0 and an optimal temperature of 40 °C for mevalonate as the substrate. The expression profiles and RNA interference of <i>TcMevK</i> indicated its critical role in controlling juvenile hormone biosynthesis, as well as its participation in the production of other terpenoids in <i>T. castaneum</i>. These findings improve our understanding of the structural and biochemical features of insect Mevk and provide a structural basis for the design of MevK inhibitors. |
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spelling | doaj.art-8a19c1607d004adf9bec59b69eded6052024-03-12T16:45:25ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672024-02-01255255210.3390/ijms25052552Structural Characterization and Functional Analysis of Mevalonate Kinase from <i>Tribolium castaneum</i> (Red Flour Beetle)Haogang Zheng0Yuanyuan Yang1Ying Hu2Jiaxuan Shi3Qiaohui Li4Yuanqiang Wang5Qingyou Xia6Pengchao Guo7Integrative Science Center of Germplasm Creation in Western China (CHONGQING) Science City, Biological Science Research Center, Southwest University, Chongqing 400716, ChinaIntegrative Science Center of Germplasm Creation in Western China (CHONGQING) Science City, Biological Science Research Center, Southwest University, Chongqing 400716, ChinaIntegrative Science Center of Germplasm Creation in Western China (CHONGQING) Science City, Biological Science Research Center, Southwest University, Chongqing 400716, ChinaIntegrative Science Center of Germplasm Creation in Western China (CHONGQING) Science City, Biological Science Research Center, Southwest University, Chongqing 400716, ChinaIntegrative Science Center of Germplasm Creation in Western China (CHONGQING) Science City, Biological Science Research Center, Southwest University, Chongqing 400716, ChinaSchool of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing 400054, ChinaIntegrative Science Center of Germplasm Creation in Western China (CHONGQING) Science City, Biological Science Research Center, Southwest University, Chongqing 400716, ChinaIntegrative Science Center of Germplasm Creation in Western China (CHONGQING) Science City, Biological Science Research Center, Southwest University, Chongqing 400716, ChinaMevalonate kinase (MevK) is an important enzyme in the mevalonate pathway that catalyzes the phosphorylation of mevalonate into phosphomevalonate and is involved in juvenile hormone biosynthesis. Herein, we present a structure model of MevK from the red flour beetle <i>Tribolium castaneum</i> (<i>Tc</i>MevK), which adopts a compact α/β conformation that can be divided into two parts: an N-terminal domain and a C-terminal domain. A narrow, deep cavity accommodating the substrate and cofactor was observed at the junction between the two domains of <i>Tc</i>MevK. Computational simulation combined with site-directed mutagenesis and biochemical analyses allowed us to define the binding mode of <i>Tc</i>MevK to cofactors and substrates. Moreover, <i>Tc</i>MevK showed optimal enzyme activity at pH 8.0 and an optimal temperature of 40 °C for mevalonate as the substrate. The expression profiles and RNA interference of <i>TcMevK</i> indicated its critical role in controlling juvenile hormone biosynthesis, as well as its participation in the production of other terpenoids in <i>T. castaneum</i>. These findings improve our understanding of the structural and biochemical features of insect Mevk and provide a structural basis for the design of MevK inhibitors.https://www.mdpi.com/1422-0067/25/5/2552mevalonate pathwayenzymatic activityjuvenile hormone biosynthesis |
spellingShingle | Haogang Zheng Yuanyuan Yang Ying Hu Jiaxuan Shi Qiaohui Li Yuanqiang Wang Qingyou Xia Pengchao Guo Structural Characterization and Functional Analysis of Mevalonate Kinase from <i>Tribolium castaneum</i> (Red Flour Beetle) International Journal of Molecular Sciences mevalonate pathway enzymatic activity juvenile hormone biosynthesis |
title | Structural Characterization and Functional Analysis of Mevalonate Kinase from <i>Tribolium castaneum</i> (Red Flour Beetle) |
title_full | Structural Characterization and Functional Analysis of Mevalonate Kinase from <i>Tribolium castaneum</i> (Red Flour Beetle) |
title_fullStr | Structural Characterization and Functional Analysis of Mevalonate Kinase from <i>Tribolium castaneum</i> (Red Flour Beetle) |
title_full_unstemmed | Structural Characterization and Functional Analysis of Mevalonate Kinase from <i>Tribolium castaneum</i> (Red Flour Beetle) |
title_short | Structural Characterization and Functional Analysis of Mevalonate Kinase from <i>Tribolium castaneum</i> (Red Flour Beetle) |
title_sort | structural characterization and functional analysis of mevalonate kinase from i tribolium castaneum i red flour beetle |
topic | mevalonate pathway enzymatic activity juvenile hormone biosynthesis |
url | https://www.mdpi.com/1422-0067/25/5/2552 |
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