Prediction of three-dimensional structures and structural flexibilities of wild-type and mutant cytochrome P450 1A2 using molecular dynamics simulations

2016 ◽  
Vol 68 ◽  
pp. 48-56 ◽  
Author(s):  
Yurie Watanabe ◽  
Shuichi Fukuyoshi ◽  
Masahiro Hiratsuka ◽  
Noriyuki Yamaotsu ◽  
Shuichi Hirono ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Cytochrome P450 ◽  
Molecular Dynamics Simulations ◽  
Three Dimensional ◽  
Wild Type ◽  
Cytochrome P450 1A2 ◽  
Dynamics Simulations

scholarly journals Deciphering Structural Alterations Associated with Activity Reductions of Genetic Polymorphisms in Cytochrome P450 2A6 Using Molecular Dynamics Simulations

2021 ◽  
Vol 22 (18) ◽  
pp. 10119
Author(s):  
Koichi Kato ◽  
Tomoki Nakayoshi ◽  
Rika Nokura ◽  
Hiroki Hosono ◽  
Masahiro Hiratsuka ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Cytochrome P450 ◽  
Molecular Dynamics Simulations ◽  
Genetic Polymorphisms ◽  
Structural Changes ◽  
Three Dimensional ◽  
Smoking Behavior ◽  
Enzymatic Activities ◽  
Access Channel ◽  
Dynamics Simulations

Cytochrome P450 (CYP) 2A6 is a monooxygenase involved in the metabolism of various endogenous and exogenous chemicals, such as nicotine and therapeutic drugs. The genetic polymorphisms in CYP2A6 are a cause of individual variation in smoking behavior and drug toxicities. The enzymatic activities of the allelic variants of CYP2A6 were analyzed in previous studies. However, the three-dimensional structures of the mutants were not investigated, and the mechanisms underlying activity reduction remain unknown. In this study, to investigate the structural changes involved in the reduction in enzymatic activities, we performed molecular dynamics simulations for ten allelic mutants of CYP2A6. For the calculated wild type structure, no significant structural changes were observed in comparison with the experimental structure. On the other hand, the mutations affected the interaction with heme, substrates, and the redox partner. In CYP2A6.44, a structural change in the substrate access channel was also observed. Those structural effects could explain the alteration of enzymatic activity caused by the mutations. The results of simulations provide useful information regarding the relationship between genotype and phenotype.

scholarly journals Lipid molecules can induce an opening of membrane-facing tunnels in cytochrome P450 1A2

2016 ◽  
Vol 18 (44) ◽  
pp. 30344-30356 ◽  
Author(s):  
Petr Jeřábek ◽  
Jan Florián ◽  
Václav Martínek
Keyword(s):  
Molecular Dynamics ◽  
Aqueous Solution ◽  
Cytochrome P450 ◽  
Molecular Dynamics Simulations ◽  
Coarse Grained ◽  
Cytochrome P450 1A2 ◽  
Structure And Dynamics ◽  
Human Cytochrome ◽  
Membrane Bound ◽  
Dynamics Simulations

The structure and dynamics of the membrane-bound full-length human cytochrome P450 1A2 (CYP1A2) in aqueous solution determined by coarse-grained and all-atom molecular dynamics simulations.

scholarly journals Free energies of binding of R- and S-propranolol to wild-type and F483A mutant cytochrome P450 2D6 from molecular dynamics simulations

2007 ◽  
Vol 36 (6) ◽  
pp. 589-599 ◽  
Author(s):  
Chris de Graaf ◽  
Chris Oostenbrink ◽  
Peter H. J. Keizers ◽  
Barbara M. A. van Vugt-Lussenburg ◽  
Jan N. M. Commandeur ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Cytochrome P450 ◽  
Molecular Dynamics Simulations ◽  
Cytochrome P450 2D6 ◽  
Free Energies ◽  
Wild Type ◽  
Dynamics Simulations ◽  
P450 2D6

scholarly journals Exploration of the cofactor specificity of wild-type phosphite dehydrogenase and its mutant using molecular dynamics simulations

RSC Advances ◽  
2021 ◽  
Vol 11 (24) ◽  
pp. 14527-14533
Author(s):  
Kunlu Liu ◽  
Min Wang ◽  
Yubo Zhou ◽  
Hongxiang Wang ◽  
Yudong Liu ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Wild Type ◽  
Cofactor Specificity ◽  
Phosphite Dehydrogenase ◽  
Dynamics Simulations

Phosphite dehydrogenase (Pdh) catalyzes the NAD-dependent oxidation of phosphite to phosphate with the formation of NADH.

Observation of “Ionic Lock” Formation in Molecular Dynamics Simulations of Wild-Type β1and β2Adrenergic Receptors

Biochemistry ◽  
2009 ◽  
Vol 48 (22) ◽  
pp. 4789-4797 ◽  
Author(s):  
Stefano Vanni ◽  
Marilisa Neri ◽  
Ivano Tavernelli ◽  
Ursula Rothlisberger
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Wild Type ◽  
Dynamics Simulations
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