Molecular modeling of the lipase-catalyzed hydrolysis of acetoxymethyl(i-propoxy)phenylphosphine oxide and its P-borane analogue

Crystal and molecular structure of hexagonal form of lipase B from Candida antarctica.

“…Of particular concern, in one of our ongoing research projects, is the kinetic resolution of racemic P-stereogenic alkoxy(hydroxymethyl)phenylphosphine oxides and P-stereogenic alkoxy(hydroxymethyl)phenylphosphine P-boranes via their enzymatic acetylation . Recently, we reported the results of molecular modeling of the hydrolysis reactions of acetoxymethyl(ipropoxy)-phenylphosphine oxide and its P-borane analogue, acetoxymethyl(i-propoxy)-phenylphosphine P-borane, promoted by the CAL-B enzyme (Krasiński et al, 2012). These theoretical calculations suggested a hypothetical explanation of the stereochemistry of the observed hydrolysis reactions.…”

“…Lipases (EC 3.1.1.3) catalyze the hydrolysis of carboxylic acid esters in aqueous media but also the esterification or transesterification in organic solvents (Bornscheuer & Kazlauskas, 1999;Paravidino et al, 2012;Singh et al, 2012). The studies on applying commercially available hydrolytic enzymes, including lipase B from Candida antarctica (CAL-B), Candida rugosa lipase (CRL), lipase PS Amano, AK Amano, AH Amano or lipoprotein lipase (LPL), to the synthesis of chiral non-racemic heteroorganic compounds, have been carried out in our Department for many years (Kaczmarczyk et al, 2011;Kiełbasiński et al, 2003;Kiełbasiński & Mikołajczyk, 2007;Krasiński et al, 2012;Kwiatkowska et al, 2011;Rachwalski et al, 2008). We have decided to make theoretical (Krasiński et al, 2012) and experimental attempts to explain the catalytic mechanism of the enzymes and the nature of their promiscuous behavior.…”

“…All above mentioned structures are insufficient to explain the mechanism of action of these enzymes towards the heteroorganic substrates and their analogs which we use in enzyme-controlled chemical reactions conducted in our laboratory (Kaczmarczyk et al, 2011;Kwiatkowska et al, 2011;Krasiński et al, 2012). For that reason, the crystal structures of the enzymes in the appropriate complex forms, i.e., with the particular substrates or analogs that we use, are needed.…”

Molecular dynamics investigations of BioH protein substrate specificity for biotin synthesis

“…Structural optimizations of pimeloyl moiety or azelayl moiety linked with S35 were conducted using B3LYP combined with 6-31G* (Krasiński, Cypryk, Kwiatkowska, Mikołajczyk & Kiełbasiński, 2012;Xu, Meher, Eustache & Wang, 2014) basis set using the Gaussian09 software. RESP fitting procedure was used for charge derivation based on the optimal geometry.…”

Bioinformatics and Computational Biology in Poland

“…Wiesław Nowak at the Nicolaus Copernicus University (NCU) in Toruń is working in the area of biomolecular simulations of conformational transitions and interactions of enzymes with small molecules [97]. A group headed by Marek Cypryk at the Centre of Molecular and Macromolecular Studies PAS in Łódź is working, i.a., on computational chemistry and modeling of the chemical reaction systems [98]. Groups led by Dariusz Matosiuk and Krzysztof Jóźwiak at the Medical University of Lublin extensively use methods of bioinformatics and cheminformatics for modeling of proteins, in particular membrane receptors, and their interactions with small molecule ligands [99], [100].…”