Insights into the Chemical Reactivity in Acetyl-CoA Synthase
| Autor: | Shi-Lu Chen, Per E. M. Siegbahn |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Iron-Sulfur Proteins
Reaction mechanism Stereochemistry Acetate-CoA Ligase Firmicutes chemistry.chemical_element 010402 general chemistry 01 natural sciences Catalysis Inorganic Chemistry chemistry.chemical_compound Bacterial Proteins Nickel Moorella Physical and Theoretical Chemistry Density Functional Theory biology 010405 organic chemistry Acetyl-CoA Methyl radical Active site Substrate (chemistry) 0104 chemical sciences Vitamin B 12 Models Chemical chemistry biology.protein NIP Oxidation-Reduction |
| Zdroj: | Inorganic Chemistry. 59:15167-15179 |
| ISSN: | 1520-510X 0020-1669 |
| DOI: | 10.1021/acs.inorgchem.0c02139 |
| Popis: | The biological synthesis of acetyl-coenzyme A (acetyl-CoA), catalyzed by acetyl-CoA synthase (ACS), is of biological significance and chemical interest acting as a source of energy and carbon. The catalyst contains an unusual hexa-metal cluster with two nickel ions and a [Fe4S4] cluster. DFT calculations have been performed to investigate the ACS reaction mechanism starting from three different oxidation states (+2, +1, and 0) of Nip, the nickel proximal to [Fe4S4]. The results indicate that the ACS reaction proceeds first through a methyl radical transfer from cobalamin (Cbl) to Nip randomly accompanying with the CO binding. After that, C-C bond formation occurs between the Nip-bound methyl and CO, forming Nip-acetyl. The substrate CoA-S- then binds to Nip, allowing C-S bond formation between the Nip-bound acetyl and CoA-S-. Methyl transfer is rate-limiting with a barrier of ∼14 kcal/mol, which does not depend on the presence or absence of CO. Both the Nip2+ and Nip1+ states are chemically capable of catalyzing the ACS reaction independent of the state (+2 or +1) of the [Fe4S4] cluster. The [Fe4S4] cluster is not found to affect the steps of methyl transfer and C-C bond formation but may be involved in the C-S bond formation depending on the detailed mechanism chosen. An ACS active site containing a Nip(0) state could not be obtained. Optimizations always led to a Nip1+ state coupled with [Fe4S4]1+. The calculations show a comparable activity for Nip1+/[Fe4S4]1+, Nip1+/[Fe4S4]2+, and Nip2+/[Fe4S4]2+. The results here give significant insights into the chemistry of the important ACS reaction. |
| Databáze: | OpenAIRE |
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