How To Produce Methane Precursor in the Upper Ocean by An Untypical Non‐Heme Fe‐Dependent Methylphosphonate Synthase?

Abstract

A new methane formation pathway, which uses methylphosphonate (MPn) as the methane precursor, has been discovered in the upper ocean. Methylphosphonate synthase (MPnS) is a key piece in this pathway to produce MPn from 2‐hydroxyethylphosphonate (2‐HEP), using an untypical 2‐His‐1‐Gln non‐heme iron architecture. Herein, the MPnS reaction mechanism was demonstrated by the density functional calculations to mainly include the substrate hydroxyl deprotonation, the formation of a MPn radical and a formate, and the hydrogen abstraction of formate by MPn radical. The second‐shell Lys28’ may serve as a proton reservoir activating 2‐HEP and regenerating the Fe site. The Fe‐bound superoxide radical is a bifunctional species to deprotonate the substrate hydroxyl and abstract the substrate methylene hydrogen. Several alternative mechanisms have been ruled out. Furthermore, the catalytic activity of MPnS was found to be inactivated/reduced by the mutation of Gln152E/Gln152H/Gln152D, rendering a significant evolutionary advantage with an uncommon 2‐His‐1‐Gln triad introduced to the ferrous coordination sphere.

Mechanistic Insights into the Oxidative Rearrangement Catalyzed by the Unprecedented Dioxygenase ChaP Involved in Chartreusin Biosynthesis

“…In 5 IM11, the CO 2 molecule has been completely formed with a C1–C2 distance of 3.86 Å. This decarboxylation reaction was calculated to be a high exothermic process . This decarboxylation is a complex process which involves multiple changes, including the formation of a new molecule of CO 2 , the reorganization of the active site (Figure S18), the evolvement of the electronic structures, and the change of the coordination mode of the iron center.…”

The Se–S Bond Formation in the Covalent Inhibition Mechanism of SARS-CoV-2 Main Protease by Ebselen-like Inhibitors: A Computational Study

“…The best docked pose shown in Figure S11 has been used as the starting structure for the inhibition mechanism at the QM level, and geometry optimizations were performed with a B3LYP/D3 functional [88][89][90][91] and 6-31+G basis set for all the atoms as implemented in the Gaussian 09 package [92]. To quantify the ZPE corrections, frequencies were calculated at the same level of theory, excluding the contributions of frozen atoms in the vibrational analysis [93]. To evaluate the environment effects, single-point calculations B3LYP-D3/6-31+G(2d,2p) in the framework of the SMD [94] model were performed on the optimized geometries by using the dielectric constants for protein (ε = 4) and water (ε = 80).…”

Catalytic Coupling of CH4 with CO2 and CO by a Modified Human Carbonic Anhydrase Combined with Oriented External Electric Fields: Mechanistic Insights from DFT Calculations

“…It should be pointed out that some atoms are fixed at the position of the X-ray crystal structure to approximately mimic the backbone structure of a protein, and such geometrical constraints do not significantly change the ZPE correction in our calculations. The QM cluster model approach has been widely used to explore the enzymatic catalysis. − , …”

“…The QM cluster model approach has been widely used to explore the enzymatic catalysis. [30][31][32][33]43 It was noted that the gas-phase computations generally overestimate the entropic contribution to the Gibbs free energy of the reaction step with different numbers of product and reactant molecules in the enzymatic environment, and here a correction of −2.6 (or 2.6) kcal/mol was used to correct the relative free energies for the 2:1 (or 1:2) conversion on the basis of the free volume theory. 44 2.2.…”