Raman evidence for specific substrate-induced structural changes in the heme pocket of human cytochrome P450 aromatase during the three consecutive oxygen activation steps

Biochemistry
Takehiko ToshaTeizo Kitagawa

Abstract

Specific substrate-induced structural changes in the heme pocket are proposed for human cytochrome P450 aromatase (P450arom) which undergoes three consecutive oxygen activation steps. We have experimentally investigated this heme environment by resonance Raman spectra of both substrate-free and substrate-bound forms of the purified enzyme. The Fe-CO stretching mode (nu(Fe)(-)(CO)) of the CO complex and Fe(3+)-S stretching mode (nu(Fe)(-)(S)) of the oxidized form were monitored as a structural marker of the distal and proximal sides of the heme, respectively. The nu(Fe)(-)(CO) mode was upshifted from 477 to 485 and to 490 cm(-)(1) by the binding of androstenedione and 19-aldehyde-androstenedione, substrates for the first and third steps, respectively, whereas nu(Fe)(-)(CO) was not observed for P450arom with 19-hydroxyandrostenedione, a substrate for the second step, indicating that the heme distal site is very flexible and changes its structure depending on the substrate. The 19-aldehyde-androstenedione binding could reduce the electron donation from the axial thiolate, which was evident from the low-frequency shift of nu(Fe)(-)(S) by 5 cm(-)(1) compared to that of androstenedione-bound P450arom. Changes in the environment in th...Continue Reading

References

Mar 1, 1982·The Biochemical Journal·M AkhtarJ N Wright
Mar 8, 1995·Biochemical and Biophysical Research Communications·Y KimataY Ishimura
Jun 1, 1994·The Journal of Steroid Biochemistry and Molecular Biology·S E BulunE R Simpson
Mar 1, 1993·The Journal of Steroid Biochemistry and Molecular Biology·K R KorzekwaY Osawa
Mar 1, 1993·The Journal of Steroid Biochemistry and Molecular Biology·M AkhtarJ N Wright
Oct 8, 1999·Biophysical Journal·J VojtechovskýI Schlichting
Apr 7, 2005·Journal of the American Chemical Society·John C HackettChristopher M Hadad

❮ Previous
Next ❯

Citations

Jul 16, 2008·Analytical and Bioanalytical Chemistry·Emre M Isin, F Peter Guengerich
Mar 12, 2011·The Journal of Physical Chemistry. B·Venugopal KarunakaranPaul M Champion
Dec 3, 2009·The Journal of Biological Chemistry·Claire GiroudJérôme Santolini
Dec 21, 2010·Archives of Biochemistry and Biophysics·Abhinav LuthraStephen G Sligar
Nov 26, 2010·The Journal of Steroid Biochemistry and Molecular Biology·Muhammad AkhtarPeter Lee-Robichaud
Sep 22, 2010·Archives of Biochemistry and Biophysics·Roman Davydov, Brian M Hoffman
Sep 30, 2008·The Journal of Steroid Biochemistry and Molecular Biology·Todd W MillerCarlos L Arteaga
May 17, 2008·Biochemical and Biophysical Research Communications·Yelena V GrinkovaStephen G Sligar
Apr 17, 2013·Biotechnology and Applied Biochemistry·Giovanna Di Nardo, Gianfranco Gilardi
Jun 1, 2007·The Journal of Biological Chemistry·François J M Chartier, Manon Couture
Jul 3, 2017·Biochimica Et Biophysica Acta. Proteins and Proteomics·Piotr J Mak, Ilia G Denisov

❮ 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.