Four amino acids define the CO2 binding pocket of enoyl-CoA carboxylases/reductases
| Autor: | Gabriele M. M. Stoffel, Jan Zarzycki, David Adrian Saez, Bastian Vögeli, Soichi Wakatsuki, Hasan DeMirci, Esteban Vöhringer-Martinez, Tobias J. Erb, Yashas Rao, Yasuo Yoshikuni |
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| Rok vydání: | 2019 |
| Předmět: |
Models
Molecular Fatty Acid Desaturases Stereochemistry Streptomycetaceae 010402 general chemistry 01 natural sciences Biochemistry Catalysis carboxylases 03 medical and health sciences enzyme mechanisms Models Catalytic Domain MD Multidisciplinary Amino Acids 030304 developmental biology chemistry.chemical_classification 0303 health sciences CO2 fixation Multidisciplinary biology Carbon fixation RuBisCO Active site Molecular carbon dioxide Biological Sciences biology.organism_classification 0104 chemical sciences Amino acid Enzymes Enzyme chemistry Catalytic cycle 13. Climate action biology.protein Kitasatospora Carrier Proteins |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America, vol 116, iss 28 Proceedings of the National Academy of Sciences of the United States of America Proceedings of the National Academy of Sciences |
| Popis: | Significance Carboxylases capture and convert CO2, which makes them key enzymes in photosynthesis and the global carbon cycle. However, the question how enzymes bind atmospheric CO2 is still unsolved. We studied enoyl-CoA carboxylases/reductases (Ecrs), the fastest CO2-fixing enzymes in nature, using structural biology, biochemistry, and advanced computational methods. Ecrs create a highly specific CO2-binding pocket with 4 amino acids at the active site. The pocket controls the fate of the gaseous molecule during catalysis and shields the catalytic center from oxygen and water. This exquisite control makes Ecrs highly efficient carboxylases outcompeting RuBisCO, the key enzyme of photosynthesis, by an order of magnitude. Our findings define the atomic framework for the future development of CO2-converting catalysts in biology and chemistry. Carboxylases are biocatalysts that capture and convert carbon dioxide (CO2) under mild conditions and atmospheric concentrations at a scale of more than 400 Gt annually. However, how these enzymes bind and control the gaseous CO2 molecule during catalysis is only poorly understood. One of the most efficient classes of carboxylating enzymes are enoyl-CoA carboxylases/reductases (Ecrs), which outcompete the plant enzyme RuBisCO in catalytic efficiency and fidelity by more than an order of magnitude. Here we investigated the interactions of CO2 within the active site of Ecr from Kitasatospora setae. Combining experimental biochemistry, protein crystallography, and advanced computer simulations we show that 4 amino acids, N81, F170, E171, and H365, are required to create a highly efficient CO2-fixing enzyme. Together, these 4 residues anchor and position the CO2 molecule for the attack by a reactive enolate created during the catalytic cycle. Notably, a highly ordered water molecule plays an important role in an active site that is otherwise carefully shielded from water, which is detrimental to CO2 fixation. Altogether, our study reveals unprecedented molecular details of selective CO2 binding and C–C-bond formation during the catalytic cycle of nature’s most efficient CO2-fixing enzyme. This knowledge provides the basis for the future development of catalytic frameworks for the capture and conversion of CO2 in biology and chemistry. |
| Databáze: | OpenAIRE |
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