A survey of active site access channels in cytochromes P450

Journal of Inorganic Biochemistry
Rebecca C Wade Sudarko

Abstract

In cytochrome P450s, the active site is situated deep inside the protein next to the heme cofactor, and is often completely isolated from the surrounding solvent. To identify routes by which substrates may enter into and products exit from the active site, random expulsion molecular dynamics simulations were performed for three cytochrome P450s: CYP101, CYP102A1 and CYP107A1 [J. Mol. Biol. 303 (2000) 797; Proc. Natl. Acad. Sci. USA 99 (2002) 5361]. Amongst the different pathways identified, one pathway was found to be common to all three cytochrome P450s although the mechanism of ligand passage along it was different in each case and apparently adapted to the substrate specificity of the enzyme. Recently, a number of new crystal structures of cytochrome P450s have been solved. Here, we analyse the open channels leading to the active site that these structures reveal. We find that in addition to showing the common pathway, they provide experimental evidence for the existence of three additional channels that were identified by simulation. We also discuss how the location of xenon binding sites in CYP101 suggests a role for one of the pathways identified by molecular dynamics simulations as a route for gaseous species, such as ox...Continue Reading

Citations

Nov 10, 2013·Bioinformatics·Lydia BenkaidaliMichel Petitjean
Jan 28, 2014·Interdisciplinary Sciences, Computational Life Sciences·Li-Na MaDong-Qing Wei
May 17, 2011·Biochemistry·Phaneeswara-Rao KommojuMarilyn Schuman Jorns
Sep 4, 2009·Journal of Molecular Modeling·Navaneethakrishnan KrishnamoorthyKeun Woo Lee
May 4, 2012·Nucleic Acids Research·Karel BerkaMichal Otyepka
Jul 16, 2008·Analytical and Bioanalytical Chemistry·Emre M Isin, F Peter Guengerich
Jul 30, 2010·Plant Molecular Biology·Leeann E ThorntonMichael M Neff
Aug 21, 2013·Journal of Cheminformatics·David SehnalJaroslav Koča
Mar 25, 2014·FEBS Letters·Nathalie Colloc'h, Thierry Prangé
Jul 9, 2013·Protein Science : a Publication of the Protein Society·Shabana VohraPhilip C Biggin
Sep 10, 2009·Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology·Wenfu MaoMay R Berenbaum
Jun 27, 2009·Pharmacology & Therapeutics·Ilia G DenisovStephen G Sligar
Apr 9, 2008·Biophysical Chemistry·Rabindra Kumar Behera, Shyamalava Mazumdar
Nov 23, 2007·Journal of Biochemical and Biophysical Methods·Xinli LiuHuangliang Jiang
Jul 20, 2005·EMBO Reports·Karin SchleinkoferRebecca C Wade
Oct 24, 2015·Biochimica Et Biophysica Acta·Xiaofeng YuRebecca C Wade
Oct 25, 2007·Proteins·Eva StjernschantzChris Oostenbrink
Sep 7, 2007·Proteins·Oliver Carrillo, Modesto Orozco
Apr 3, 2007·Protein Science : a Publication of the Protein Society·Liliane MouawadDaniel Lavalette
Jan 22, 2013·Journal of Molecular Recognition : JMR·Maria S ZharkovaAlexander I Archakov
Mar 2, 2011·Journal of Molecular Recognition : JMR·Ting Wang, Yong Duan
Jun 29, 2010·Pest Management Science·Robert T JonesJean M H van den Elsen
Mar 9, 2005·Biophysical Chemistry·Chandra S Verma, Stefan Fischer
Mar 19, 2016·Journal of Chemical Theory and Computation·Jakub Mateusz Rydzewski, Wieslaw Nowak
Oct 31, 2006·Biochimica Et Biophysica Acta·Michal OtyepkaPavel Anzenbacher
Aug 22, 2006·Biochimica Et Biophysica Acta·Vlad CojocaruRebecca C Wade
May 13, 2006·Nitric Oxide : Biology and Chemistry·Clément GautierAnny Slama-Schwok
Oct 18, 2005·Biochimica Et Biophysica Acta·Rebecca C WadeChristiane Jung
Oct 3, 2015·The Journal of Chemical Physics·J Rydzewski, W Nowak
May 31, 2015·Biochimica Et Biophysica Acta·Ying-Lu CuiHong-Xing Zhang
Apr 14, 2016·Biophysical Journal·Dmitri R DavydovWayne L Hubbell
Nov 27, 2014·Journal of Molecular Graphics & Modelling·Nathan DesdouitsArnaud Blondel
Sep 29, 2011·Biophysical Journal·Yinglong Miao, Jerome Baudry

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.