Abstract
The enzymatic hydration of CO2 into HCO3 − by carbonic anhydrase (CA) is highly efficient and environment-friendly measure for CO2 sequestration. Here extensive MM MD and QM/MM MD simulations were used to explore the whole enzymatic process, and a full picture of the enzymatic hydration of CO2 by CA was achieved. Prior to CO2 hydration, the proton transfer from the water molecule (WT1) to H64 is the rate-limiting step with the free energy barrier of 10.4 kcal/mol, which leads to the ready state with the Zn-bound OH−. The nucleophilic attack of OH− on CO2 produces HCO3 − with the free energy barrier of 4.4 kcal/mol and the free energy release of about 8.0 kcal/mol. Q92 as the key residue manipulates both CO2 transportation to the active site and release of HCO3 −. The unprotonated H64 in CA prefers in an inward orientation, while the outward conformation is favorable energetically for its protonated counterpart. The conformational transition of H64 between inward and outward correlates with its protonation state, which is mediated by the proton transfer and the product release. The whole enzymatic cycle has the free energy span of 10.4 kcal/mol for the initial proton transfer step and the free energy change of −6.5 kcal/mol. The mechanistic details provide a comprehensive understanding of the entire reversible conversion of CO2 into bicarbonate and roles of key residues in chemical and nonchemical steps for the enzymatic hydration of CO2.
Highlights
CO2 reduction and carbon neutral have been constantly drawing attention in human societies
The representative structure selected from the MD simulation and the QM region highlighted in the stick model are displayed in Figure 4, where the zinc ion is coordinated with three histidines (H94, H96, and H119) and one water molecule, and the residue H64 is stable at the inward conformation
Extensive QM(B3LYP)/MM MD and MM MD simulations with the umbrella sampling have been used to study the whole enzymatic hydration of CO2 by carbonic anhydrase, including the CO2 delivery to the active site, the catalytic mechanisms for proton transfer and CO2 hydration, the dissociation and release of HCO3−, the conformational change of H64 side chain, and the role of key residues
Summary
CO2 reduction and carbon neutral have been constantly drawing attention in human societies. According to the high-resolution crystal structure and the previous studies (Roy and Taraphder, 2009), the dihedral angle χ (N–Cα–Cβ–Cc) was defined as the reaction coordinate (RC2, see Figure 3B), which changes from 43.87° to −38.40° with a 3° interval for two adjacent windows in the 25 ns MD simulation with a force constant of 200 kcal/mol rad (Sanz-Pérez et al, 2016), describing the conformational transition of H64 from inward to outward orientation.
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