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</...

Full description

Bibliographic Details
Main Authors: Haogang Zheng, Yuanyuan Yang, Ying Hu, Jiaxuan Shi, Qiaohui Li, Yuanqiang Wang, Qingyou Xia, Pengchao Guo
Format: Article
Language:English
Published: MDPI AG 2024-02-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/25/5/2552
_version_ 1797264452726292480
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.
first_indexed 2024-04-25T00:29:08Z
format Article
id doaj.art-8a19c1607d004adf9bec59b69eded605
institution Directory Open Access Journal
issn 1661-6596
1422-0067
language English
last_indexed 2024-04-25T00:29:08Z
publishDate 2024-02-01
publisher MDPI AG
record_format Article
series International Journal of Molecular Sciences
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
work_keys_str_mv AT haogangzheng structuralcharacterizationandfunctionalanalysisofmevalonatekinasefromitriboliumcastaneumiredflourbeetle
AT yuanyuanyang structuralcharacterizationandfunctionalanalysisofmevalonatekinasefromitriboliumcastaneumiredflourbeetle
AT yinghu structuralcharacterizationandfunctionalanalysisofmevalonatekinasefromitriboliumcastaneumiredflourbeetle
AT jiaxuanshi structuralcharacterizationandfunctionalanalysisofmevalonatekinasefromitriboliumcastaneumiredflourbeetle
AT qiaohuili structuralcharacterizationandfunctionalanalysisofmevalonatekinasefromitriboliumcastaneumiredflourbeetle
AT yuanqiangwang structuralcharacterizationandfunctionalanalysisofmevalonatekinasefromitriboliumcastaneumiredflourbeetle
AT qingyouxia structuralcharacterizationandfunctionalanalysisofmevalonatekinasefromitriboliumcastaneumiredflourbeetle
AT pengchaoguo structuralcharacterizationandfunctionalanalysisofmevalonatekinasefromitriboliumcastaneumiredflourbeetle