Structural Basis for the Mechanism of ATP-Dependent Acetone Carboxylation
- Washington State Univ., Pullman, WA (United States)
- Montana State Univ., Bozeman, MT (United States)
- Imperial College, London (United Kingdom)
- Argonne National Lab. (ANL), Argonne, IL (United States)
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 frst structural rationale for acetone carboxylation is presented here, focusing on the 360kDa ($αβγ$)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 signifcance to the global carbon cycle.
- Research Organization:
- Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS); Montana State Univ., Bozeman, MT (United States)
- Sponsoring Organization:
- USDOE Office of Science (SC), Basic Energy Sciences (BES); USDOE Office of Science (SC), Biological and Environmental Research (BER); National Institutes of Health (NIH); National Institute of General Medical Sciences (NIGMS)
- Grant/Contract Number:
- AC02-06CH11357; FG02-04ER15563
- OSTI ID:
- 1624314
- Journal Information:
- Scientific Reports, Vol. 7, Issue 1; ISSN 2045-2322
- Publisher:
- Nature Publishing GroupCopyright Statement
- Country of Publication:
- United States
- Language:
- English
Web of Science
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