Human cytochrome P450 2D6 (CYP2D6) is an enzyme of the CYP superfamily responsible for biotransformation of about 20% of drugs of known metabolism containing a basic nitrogen and a planar aromatic ring. Here, we present a combined experimental and computational study on the compressibility and flexibility of unliganded and quinidine-bound CYP2D6. Experimentally, high-pressure induced Soret band shifts of the enzyme were measured by UV/VIS spectroscopy, while 100 ns all atomic molecular dynamics (MD) simulations in explicit water were used in the computational analysis. We identified sharp differences between ligand-free and quinidine-bound CYP2D6 forms in compressibility, flexibility parameters and active site solvation. While the unliganded CYP2D6 is compressible, quinidine binding significantly rigidifies the CYP2D6 active site. In addition, MD simulations show that quinidine binding results in pronounced reductions in active site flexibility and solvation.
- Publication type
- Meeting Abstract MeSH
Biomolecular channels play important roles in many biological systems, e.g. enzymes, ribosomes and ion channels. This article introduces a web-based interactive MOLEonline 2.0 application for the analysis of access/egress paths to interior molecular voids. MOLEonline 2.0 enables platform-independent, easy-to-use and interactive analyses of (bio)macromolecular channels, tunnels and pores. Results are presented in a clear manner, making their interpretation easy. For each channel, MOLEonline displays a 3D graphical representation of the channel, its profile accompanied by a list of lining residues and also its basic physicochemical properties. The users can tune advanced parameters when performing a channel search to direct the search according to their needs. The MOLEonline 2.0 application is freely available via the Internet at http://ncbr.muni.cz/mole or http://mole.upol.cz.
- MeSH
- Cytochrome P-450 CYP3A chemistry MeSH
- Enzymes chemistry MeSH
- Internet MeSH
- Ion Channels chemistry MeSH
- Protein Conformation MeSH
- Models, Molecular MeSH
- Computer Graphics MeSH
- Ribosomes chemistry MeSH
- Software MeSH
- User-Computer Interface MeSH
- Ribosome Subunits, Large, Archaeal chemistry MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- MeSH
- Amino Acids chemistry MeSH
- Proteins chemistry MeSH
- Protein Folding MeSH
- Protein Structure, Secondary MeSH
- Thermodynamics MeSH
- Publication type
- Journal Article MeSH
- Comment MeSH
1. vyd. 162 s. : tab. ; 21 cm
- Conspectus
- Věda. Všeobecnosti. Základy vědy a kultury. Vědecká práce
- NML Fields
- věda a výzkum
