Exhaustive computational search of ionic-charge clusters that mediate interactions between mammalian cytochrome P450 (CYP) and P450-oxidoreductase (POR) proteins

Computational Biology and Chemistry
Alexander ZawairaJonathan Blackburn

Abstract

In this work, a model for the interaction between CYP2B4 and the FMN domain of rat P450-oxidoreductase is built using as template the structure of a bacterial redox complex. Amino acid residues identified in the literature as cytochrome P450 (CYP)-redox partner interfacial residues map to the interface in our model. Our model supports the view that the bacterial template represents a specific electron transfer complex and moreover provides a structural framework for explaining previous experimental data. We have used our model in an exhaustive search for complementary pairs of mammalian CYP and P450-oxidoreductase (POR) charge clusters. We quantitatively show that among the previously defined basic clusters, the 433K-434R cluster is the most dominant (32.3% of interactions) and among the acidic clusters, the 207D-208D-209D cluster is the most dominant (29%). Our analysis also reveals the previously not described basic cluster 343R-345K (16.1% of interactions) and 373K (3.2%) and the acidic clusters 113D-115E-116E (25.8%), 92E-93E (12.9%), 101D (3.2%) and 179E (3.2%). Cluster pairings among the previously defined charge clusters include the pairing of cluster 421K-422R to cluster 207D-208D-209D. Moreover, 433K-434R and 207D-208D...Continue Reading

References

Nov 27, 1979·Biochemistry·J StonehuernerF Millett
Dec 20, 1990·Journal of Molecular Biology·A HorovitzA R Fersht
Jun 5, 1987·Journal of Molecular Biology·T L PoulosA J Howard
Feb 1, 1995·Protein Engineering·A C WallaceJ M Thornton
Feb 1, 1995·Nature Structural Biology·C D WaldburgerR T Sauer
Jan 1, 1996·Journal of Structural Biology·M Totrov, R Abagyan
Aug 5, 1997·Proceedings of the National Academy of Sciences of the United States of America·M WangJ J Kim
Mar 26, 1998·Journal of Molecular Biology·R M JacksonM J Sternberg
Nov 12, 1998·Trends in Biochemical Sciences·F JeanmouginT J Gibson
Feb 27, 1999·Protein Science : a Publication of the Protein Society·Q ZhaoH P Driessen
Mar 3, 1999·Proceedings of the National Academy of Sciences of the United States of America·I F SevrioukovaT L Poulos
Mar 29, 2003·Journal of Molecular Biology·George I MakhatadzeSusan T Thomas
Jun 5, 2003·FEBS Letters·Yanay Ofran, Burkhard Rost
Dec 17, 2003·The Journal of Biological Chemistry·Guillaume A SchochEric F Johnson
Jun 8, 2004·The Journal of Biological Chemistry·Michael R WesterEric F Johnson
Jun 25, 2004·Nucleic Acids Research·Yuzhen Ye, Adam Godzik
Jul 20, 2004·The Journal of Biological Chemistry·Jason K YanoEric F Johnson
Feb 16, 2005·Biochemistry·Rusty W KelleyWayne L Backes
Apr 2, 2005·Protein Science : a Publication of the Protein Society·Chu WangDavid Baker
Jun 28, 2005·Proteins·Andrei Tovchigrechko, Ilya A Vakser
Jul 18, 2006·Nucleic Acids Research·Andrey Tovchigrechko, Ilya A Vakser
Oct 4, 2006·Biochimica Et Biophysica Acta·Andrey KaryakinChristiane Jung
Feb 22, 2007·The Journal of Biological Chemistry·Stefaan SansenEric F Johnson
Jun 23, 2007·Nucleic Acids Research·K G TinaN Srinivasan
Aug 10, 2007·Molecular Pharmacology·Lian WeiTimothy S Tracy
Aug 20, 2008·Bioinformatics·Vinay PulimJadwiga Bienkowska
Feb 25, 2009·Bioinformation·Susan CostantiniAngelo M Facchiano

❮ 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.