Dissecting the Structural Plasticity and Dynamics of Cytochrome P450 2B4 by Molecular Dynamics Simulations

2020 ◽  
Vol 60 (10) ◽  
pp. 5026-5035
Author(s):  
Junhao Li ◽  
Yang Zhou ◽  
Yun Tang ◽  
Weihua Li ◽  
Yaoquan Tu
Keyword(s):  
Molecular Dynamics ◽  
Cytochrome P450 ◽  
Molecular Dynamics Simulations ◽  
Structural Plasticity ◽  
Cytochrome P450 2B4 ◽  
Dynamics Simulations

scholarly journals Molecular Dynamics Simulations of a Cytochrome P450 from Tepidiphilus thermophilus (P450-TT) Reveal How Its Substrate-Binding Channel Opens

Molecules ◽  
2021 ◽  
Vol 26 (12) ◽  
pp. 3614
Author(s):  
Abayomi S. Faponle ◽  
Anupom Roy ◽  
Ayodeji A. Adelegan ◽  
James W. Gauld
Keyword(s):  
Crystal Structure ◽  
Molecular Dynamics ◽  
Cytochrome P450 ◽  
Amino Acid ◽  
Molecular Dynamics Simulations ◽  
Organic Molecules ◽  
Side Chain ◽  
Relative Solvent Accessibility ◽  
Amino Acid Residues ◽  
Dynamics Simulations

Cytochrome P450s (P450) are important enzymes in biology with useful biochemical reactions in, for instance, drug and xenobiotics metabolisms, biotechnology, and health. Recently, the crystal structure of a new member of the CYP116B family has been resolved. This enzyme is a cytochrome P450 (CYP116B46) from Tepidiphilus thermophilus (P450-TT) and has potential for the oxy-functionalization of organic molecules such as fatty acids, terpenes, steroids, and statins. However, it was thought that the opening to its hitherto identified substrate channel was too small to allow organic molecules to enter. To investigate this, we performed molecular dynamics simulations on the enzyme. The results suggest that the crystal structure is not relaxed, possibly due to crystal packing effects, and that its tunnel structure is constrained. In addition, the simulations revealed two key amino acid residues at the mouth of the channel; a glutamyl and an arginyl. The glutamyl’s side chain tightens and relaxes the opening to the channel in conjunction with the arginyl’s, though the latter’s side chain is less dramatically changed after the initial relaxation of its conformations. Additionally, it was observed that the effect of increased temperature did not considerably affect the dynamics of the enzyme fold, including the relative solvent accessibility of the amino acid residues that make up the substrate channel wall even as compared to the changes that occurred at room temperature. Interestingly, the substrate channel became distinguishable as a prominent tunnel that is likely to accommodate small- to medium-sized organic molecules for bioconversions. That is, P450-TT has the ability to pass appropriate organic substrates to its active site through its elaborate substrate channel, and notably, is able to control or gate any molecules at the opening to this channel.

Sign in / Sign up

Export Citation Format

Share Document