Quantum mechanical/molecular mechanical study of mechanisms of heme degradation by the enzyme heme oxygenase: the strategic function of the water cluster

Journal of the American Chemical Society
Hui ChenSason Shaik

Abstract

Heme degradation by heme oxygenase (HO) enzymes is important in maintaining iron homeostasis and prevention of oxidative stress, etc. In response to mechanistic uncertainties, we performed quantum mechanical/molecular mechanical investigations of the heme hydroxylation by HO, in the native route and with the oxygen surrogate donor H2O2. It is demonstrated that H2O2 cannot be deprotonated to yield Fe(III)OOH, and hence the surrogate reaction starts from the FeHOOH complex. The calculations show that, when starting from either Fe(III)OOH or Fe(III)HOOH, the fully concerted mechanism involving O-O bond breakage and O-C(meso) bond formation is highly disfavored. The low-energy mechanism involves a nonsynchronous, effectively concerted pathway, in which the active species undergoes first O-O bond homolysis followed by a barrier-free (small with Fe(III)HOOH) hydroxyl radical attack on the meso position of the porphyrin. During the reaction of Fe(III)HOOH, formation of the Por+*FeIV=O species, compound I, competes with heme hydroxylation, thereby reducing the efficiency of the surrogate route. All these conclusions are in accord with experimental findings (Chu, G. C.; Katakura, K.; Zhang, X.; Yoshida, T.; Ikeda-Saito, M. J. Biol. Chem...Continue Reading

References

Oct 1, 1968·Proceedings of the National Academy of Sciences of the United States of America·R TenhunenR Schmid
Jun 1, 1996·Journal of Molecular Graphics·W Smith, T R Forester
Mar 14, 1997·The Journal of Biological Chemistry·Y LiuP R Ortiz de Montellano
Sep 15, 1988·Physical Review A: General Physics·A D Becke
Aug 31, 1999·Nature Structural Biology·D J SchullerT L Poulos
Oct 8, 1999·Biophysical Journal·J VojtechovskýI Schlichting
Mar 4, 2000·Science·I SchlichtingS G Sligar
Apr 1, 2000·Current Opinion in Chemical Biology·P R Montellano
Apr 13, 2000·FEBS Letters·M SugishimaK Fukuyama
Jan 2, 2001·Journal of Inorganic Biochemistry·T Yoshida, C T Migita
Nov 7, 1996·Chemical Reviews·Masanori SonoJohn H. Dawson
Feb 21, 2002·Journal of the American Chemical Society·Roman DavydovBrian M Hoffman
Sep 19, 2002·Journal of Inorganic Biochemistry·François OgliaroSason Shaik
Dec 26, 2002·The Journal of Biological Chemistry·Latesh LadThomas L Poulos
Jun 12, 2003·Chemical Reviews·Christophe Colas, Paul R Ortiz de Montellano
Dec 18, 2003·Journal of the American Chemical Society·Sam P de VisserWalter Thiel
Mar 25, 2004·Journal of the American Chemical Society·Takashi KamachiKazunari Yoshizawa

❮ Previous
Next ❯

Citations

Mar 13, 2010·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Muhannad AltarshaWalter Thiel
Oct 29, 2013·Archives of Biochemistry and Biophysics·Angela Wilks, Geoffrey Heinzl
Feb 24, 2012·Journal of the American Chemical Society·Dandamudi UsharaniSason Shaik
Jul 27, 2011·Proceedings of the National Academy of Sciences of the United States of America·Shin-ichi J TakayamaA Grant Mauk
Mar 19, 2014·British Journal of Pharmacology·U Schatzschneider
Apr 2, 2016·The Journal of Physical Chemistry. B·Amanda B GravesMatthew Denis Liptak
Aug 5, 2016·Biochemistry·Paul A SigalaDaniel E Goldberg
Mar 30, 2017·Dalton Transactions : an International Journal of Inorganic Chemistry·Nobuhiko DojunTakeshi Uchida
Apr 13, 2017·Metallomics : Integrated Biometal Science·Matthew A CongerMatthew D Liptak
Jan 26, 2017·Dalton Transactions : an International Journal of Inorganic Chemistry·Mahin GheidiMansour Zahedi
Jun 9, 2016·Dalton Transactions : an International Journal of Inorganic Chemistry·Amanda B GravesMatthew D Liptak
Jun 13, 2018·Dalton Transactions : an International Journal of Inorganic Chemistry·Fatemeh Sadat AlaviUlf Ryde
Nov 20, 2009·Physical Chemistry Chemical Physics : PCCP·Christopher J Cramer, Donald G Truhlar
Apr 26, 2015·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Cheryl L LockhartMatthew D Liptak
Jul 25, 2012·Dalton Transactions : an International Journal of Inorganic Chemistry·Takashi KamachiKazunari Yoshizawa
Apr 15, 2020·Physical Chemistry Chemical Physics : PCCP·Chang YuanZongchao Jia
Jul 9, 2020·Physical Chemistry Chemical Physics : PCCP·Ying ZhangGuangju Chen
Sep 14, 2017·Scientific Reports·Michael J Y LeeZongchao Jia
Mar 24, 2021·Inorganic Chemistry·Tapiwa Chiura, Piotr J Mak
Mar 10, 2010·The Journal of Physical Chemistry. a·Chi Shun YeungDavid Lee Phillips
Jun 3, 2008·Journal of the American Chemical Society·Justine P Roth, Christopher J Cramer
Oct 16, 2009·Accounts of Chemical Research·Toshitaka MatsuiMasao Ikeda-Saito
Mar 25, 2009·Biochemistry·Sandip K BadyalEmma Lloyd Raven
Jul 3, 2009·The Journal of Physical Chemistry. B·Ophélie KwasnieskiEtienne Derat
Jun 8, 2012·Journal of Inorganic Biochemistry·Masaki UnnoMasao Ikeda-Saito
Dec 18, 2013·Inorganic Chemistry·Takunori UedaKoji Kano
Jul 18, 2012·The Journal of Physical Chemistry. B·Rong-Zhen Liao, Walter Thiel
Sep 7, 2012·The Journal of Physical Chemistry. B·Likai DuChengbu Liu
Apr 9, 2015·Biochemistry·Shin-Ichi J TakayamaMichael E P Murphy
May 31, 2014·Accounts of Chemical Research·Angela Wilks, Masao Ikeda-Saito
Oct 30, 2018·Chemical Reviews·Suzanne M AdamKenneth D Karlin

❮ 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.