Structural Basis for the Mechanism of ATP-Dependent Acetone Carboxylation

Abstract Microorganisms use carboxylase enzymes to form new carbon-carbon bonds by introducing carbon dioxide gas (CO2) or its hydrated form, bicarbonate (HCO3 −), into target molecules. Acetone carboxylases (ACs) catalyze the conversion of substrates acetone and HCO3 − to form the product acetoacet...

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Autores principales:	Florence Mus, Brian J. Eilers, Alexander B. Alleman, Burak V. Kabasakal, Jennifer N. Wells, James W. Murray, Boguslaw P. Nocek, Jennifer L. DuBois, John W. Peters
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/974d0ab5c0a34d4b9a8c4a31370e6562
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spelling	oai:doaj.org-article:974d0ab5c0a34d4b9a8c4a31370e65622021-12-02T11:40:15ZStructural Basis for the Mechanism of ATP-Dependent Acetone Carboxylation10.1038/s41598-017-06973-82045-2322https://doaj.org/article/974d0ab5c0a34d4b9a8c4a31370e65622017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06973-8https://doaj.org/toc/2045-2322Abstract Microorganisms use carboxylase enzymes to form new carbon-carbon bonds by introducing carbon dioxide gas (CO2) or its hydrated form, bicarbonate (HCO3 −), into target molecules. Acetone carboxylases (ACs) catalyze the conversion of substrates acetone and HCO3 − to form the product acetoacetate. Many bicarbonate-incorporating carboxylases rely on the organic cofactor biotin for the activation of bicarbonate. ACs contain metal ions but not organic cofactors, and use ATP to activate substrates through phosphorylation. How the enzyme coordinates these phosphorylation events and new C-C bond formation in the absence of biotin has remained a mystery since these enzymes were discovered. The first structural rationale for acetone carboxylation is presented here, focusing on the 360 kDa (αβγ)2 heterohexameric AC from Xanthobacter autotrophicus in the ligand-free, AMP-bound, and acetate coordinated states. These structures suggest successive steps in a catalytic cycle revealing that AC undergoes large conformational changes coupled to substrate activation by ATP to perform C-C bond ligation at a distant Mn center. These results illustrate a new chemical strategy for the conversion of CO2 into biomass, a process of great significance to the global carbon cycle.Florence MusBrian J. EilersAlexander B. AllemanBurak V. KabasakalJennifer N. WellsJames W. MurrayBoguslaw P. NocekJennifer L. DuBoisJohn W. PetersNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Florence Mus Brian J. Eilers Alexander B. Alleman Burak V. Kabasakal Jennifer N. Wells James W. Murray Boguslaw P. Nocek Jennifer L. DuBois John W. Peters Structural Basis for the Mechanism of ATP-Dependent Acetone Carboxylation
description	Abstract Microorganisms use carboxylase enzymes to form new carbon-carbon bonds by introducing carbon dioxide gas (CO2) or its hydrated form, bicarbonate (HCO3 −), into target molecules. Acetone carboxylases (ACs) catalyze the conversion of substrates acetone and HCO3 − to form the product acetoacetate. Many bicarbonate-incorporating carboxylases rely on the organic cofactor biotin for the activation of bicarbonate. ACs contain metal ions but not organic cofactors, and use ATP to activate substrates through phosphorylation. How the enzyme coordinates these phosphorylation events and new C-C bond formation in the absence of biotin has remained a mystery since these enzymes were discovered. The first structural rationale for acetone carboxylation is presented here, focusing on the 360 kDa (αβγ)2 heterohexameric AC from Xanthobacter autotrophicus in the ligand-free, AMP-bound, and acetate coordinated states. These structures suggest successive steps in a catalytic cycle revealing that AC undergoes large conformational changes coupled to substrate activation by ATP to perform C-C bond ligation at a distant Mn center. These results illustrate a new chemical strategy for the conversion of CO2 into biomass, a process of great significance to the global carbon cycle.
format	article
author	Florence Mus Brian J. Eilers Alexander B. Alleman Burak V. Kabasakal Jennifer N. Wells James W. Murray Boguslaw P. Nocek Jennifer L. DuBois John W. Peters
author_facet	Florence Mus Brian J. Eilers Alexander B. Alleman Burak V. Kabasakal Jennifer N. Wells James W. Murray Boguslaw P. Nocek Jennifer L. DuBois John W. Peters
author_sort	Florence Mus
title	Structural Basis for the Mechanism of ATP-Dependent Acetone Carboxylation
title_short	Structural Basis for the Mechanism of ATP-Dependent Acetone Carboxylation
title_full	Structural Basis for the Mechanism of ATP-Dependent Acetone Carboxylation
title_fullStr	Structural Basis for the Mechanism of ATP-Dependent Acetone Carboxylation
title_full_unstemmed	Structural Basis for the Mechanism of ATP-Dependent Acetone Carboxylation
title_sort	structural basis for the mechanism of atp-dependent acetone carboxylation
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/974d0ab5c0a34d4b9a8c4a31370e6562
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Structural Basis for the Mechanism of ATP-Dependent Acetone Carboxylation

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