MMOD-induced structural changes of hydroxylase in soluble methane monooxygenase
Abstract
Soluble methane monooxygenase in methanotrophs converts methane to methanol under ambient conditions. The maximum catalytic activity of hydroxylase (MMOH) is achieved through the interplay of its regulatory protein (MMOB) and reductase. An additional auxiliary protein, MMOD, functions as an inhibitor of MMOH; however, its inhibitory mechanism remains unknown. Here, we report the crystal structure of the MMOH-MMOD complex from Methylosinus sporium strain 5 (2.6 Å). Its structure illustrates that MMOD associates with the canyon region of MMOH where MMOB binds. Although MMOD and MMOB recognize the same binding site, each binding component triggers different conformational changes toward MMOH, which then respectively lead to the inhibition and activation of MMOH. Particularly, MMOD binding perturbs the di-iron geometry by inducing two major MMOH conformational changes, i.e., MMOH β subunit disorganization and subsequent His147 dissociation with Fe1 coordination. Furthermore, 1,6-hexanediol, a mimic of the products of sMMO, reveals the substrate access route.
- Authors:
-
- Univ. of Michigan, Ann Arbor, MI (United States)
- Chonbuk National Univ., Jeonju (Republic of Korea)
- Publication Date:
- Research Org.:
- Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
- Sponsoring Org.:
- National Research Foundation of Korea (NRF); The Biomedical Research Council (BMRC)
- OSTI Identifier:
- 1593446
- Grant/Contract Number:
- NRF-2015M3D3A1A01064876; R01 DK111465
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Science Advances
- Additional Journal Information:
- Journal Volume: 5; Journal Issue: 10; Journal ID: ISSN 2375-2548
- Publisher:
- AAAS
- Country of Publication:
- United States
- Language:
- ENGLISH
- Subject:
- 37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
Citation Formats
Kim, Hanseong, An, Sojin, Park, Yeo Reum, Jang, Hara, Yoo, Heeseon, Park, Sang Ho, Lee, Seung Jae, and Cho, Uhn-Soo. MMOD-induced structural changes of hydroxylase in soluble methane monooxygenase. United States: N. p., 2019.
Web. doi:10.1126/sciadv.aax0059.
Kim, Hanseong, An, Sojin, Park, Yeo Reum, Jang, Hara, Yoo, Heeseon, Park, Sang Ho, Lee, Seung Jae, & Cho, Uhn-Soo. MMOD-induced structural changes of hydroxylase in soluble methane monooxygenase. United States. https://doi.org/10.1126/sciadv.aax0059
Kim, Hanseong, An, Sojin, Park, Yeo Reum, Jang, Hara, Yoo, Heeseon, Park, Sang Ho, Lee, Seung Jae, and Cho, Uhn-Soo. Wed .
"MMOD-induced structural changes of hydroxylase in soluble methane monooxygenase". United States. https://doi.org/10.1126/sciadv.aax0059. https://www.osti.gov/servlets/purl/1593446.
@article{osti_1593446,
title = {MMOD-induced structural changes of hydroxylase in soluble methane monooxygenase},
author = {Kim, Hanseong and An, Sojin and Park, Yeo Reum and Jang, Hara and Yoo, Heeseon and Park, Sang Ho and Lee, Seung Jae and Cho, Uhn-Soo},
abstractNote = {Soluble methane monooxygenase in methanotrophs converts methane to methanol under ambient conditions. The maximum catalytic activity of hydroxylase (MMOH) is achieved through the interplay of its regulatory protein (MMOB) and reductase. An additional auxiliary protein, MMOD, functions as an inhibitor of MMOH; however, its inhibitory mechanism remains unknown. Here, we report the crystal structure of the MMOH-MMOD complex from Methylosinus sporium strain 5 (2.6 Å). Its structure illustrates that MMOD associates with the canyon region of MMOH where MMOB binds. Although MMOD and MMOB recognize the same binding site, each binding component triggers different conformational changes toward MMOH, which then respectively lead to the inhibition and activation of MMOH. Particularly, MMOD binding perturbs the di-iron geometry by inducing two major MMOH conformational changes, i.e., MMOH β subunit disorganization and subsequent His147 dissociation with Fe1 coordination. Furthermore, 1,6-hexanediol, a mimic of the products of sMMO, reveals the substrate access route.},
doi = {10.1126/sciadv.aax0059},
journal = {Science Advances},
number = 10,
volume = 5,
place = {United States},
year = {2019},
month = {10}
}
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