Multiscale Simulations on the Catalytic Plasticity of CYP76AH1

The catalytic promiscuity and fidelity of cytochrome P450 enzymes are widespread in the skeletal modification of terpenoid natural products and have attracted much attention. CYP76AH1 is involved in key modification reactions in the biosynthetic pathway of tanshinone, a well-known medicinal norditerpenoid. In this work, classical molecular dynamic simulations, metadynamics, and DFT calculations were performed to investigate the protein conformational dynamics, ligand binding poses, and catalytic reaction mechanism in wide-type and mutant CYP76AH1. Our results not only reveal a plausible enzymatic mechanism for mutant CYP76AH1 leading to various products but also provide valuable guidance for rational protein engineering of the CYP76 family.

Synthesis of YFeO3-δ and LaFeO3-δ Perovskites with High Catalytic Activity in Carbon Oxidation Reactions

YFeO3-δ (δ = 0.26) and LaFeO3-δ (δ = 0.5) perovskites with a high specific surface and oxygen non-stoichiometry was firstly synthesized by pyrolysis of polymer-salt compositions. It was shown that the catalytic oxidation of carbon in the presence of these complex oxide systems proceeds in the range of 400 - 700 °С, with a maximum temperature at 556 °С for YFeO3-δ; and 380 - 620 °С ,with a maximum temperature at 501 °С for LaFeO3-δ, in one-stage mode for both. By means of thermal analysis and diffractometry, it was shown that there is no contribution to the soot oxidation mechanism by cyclic perovskite surface transformations, due to the reduction of metal oxides by the soot and their subsequent reoxidation. It has been established that the basis of the catalytic reaction mechanism for both perovskites is the presence of oxygen vacancies on the surface of complex oxides.

Histidine protonation states are key in the LigI catalytic reaction mechanism

Lignin is one of the world’s most abundant organic polymers, and 2-pyrone-4,6-dicarboxylate lactonase (LigI) catalyzes the hydrolysis of 2-pyrone-4,6-dicarboxylate (PDC) in the degradation of lignin. The pH has profound effects on enzyme catalysis and therefore we studied this in the context of LigI. We found that changes of the pH mostly affects surface residues, while the residues at the active site are more subject to changes of the surrounding microenvironment. In accordance with this, a high pH facilitates the deprotonation of the substrate. Detailed free energy calculations by the empirical valence bond (EVB) approach revealed that the overall hydrolysis reaction is more likely when the three active site histidines (His31, His33 and His180) are protonated at the ɛ site, however, protonation at the δ site may be favored during specific steps of reaction. Our studies have uncovered the determinant role of the protonation state of the active site residues His31, His33 and His180 in the hydrolysis of PDC.

Catalytic mechanism of the colistin resistance protein MCR-1

Elucidation of the catalytic reaction mechanism of MCR-1 enzyme, responsible for the antimicrobial resistance to colistin, using DFT calculations on cluster models.