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Redox Reactions of NO and O2 in Iron Enzymes: A Density Functional Theory Study
Stockholm University, Faculty of Science, Department of Physics.
2006 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

In the present thesis the density functional B3LYP has been used to study reactions of NO and O2 in redox active enzymes.

Reduction of nitric oxide (NO) to nitrous oxide (N2O) is an important part in the bacterial energy conservation (denitrification). The reduction of NO in three different bimetallic active sites leads to the formation of hyponitrous acid anhydride (N2O22-). The stability of this intermediate is crucial for the reaction rate. In the two diiron systems, respiratory and scavenging types of NOR, it is possible to cleave the N-O bond, forming N2O, without any extra protons or electrons. In a heme-copper oxidase, on the other hand, both a proton and an electron are needed to form N2O.

In addition to being an intermediate in the denitrification, NO is a toxic agent. Myoglobin in the oxy-form reacts with NO forming nitrate (NO3 -) at a high rate, which should make this enzyme an efficient NO scavenger. Peroxynitrite (ONOO-) is formed as a short-lived intermediate and isomerizes to nitrate through a radical reaction.

In the mechanism for pumping protons in cytochrome oxidase, thermodynamics, rather than structural changes, might guide protons to the heme propionate for further translocation.

The dioxygenation of arachidonic acid in prostaglandin endoperoxide H synthase forms the bicyclic prostaglandin G2, through a cascade of radical reactions. The mechanism proposed by Hamberg and Samuelsson is energetically feasible.

Place, publisher, year, edition, pages
Stockholm: Fysikum , 2006. , 79 p.
Keyword [en]
enzyme catalysis, redox reactions, cytochrome oxidase, nitric oxide reductase, hyponitrous acid anhydride, peroxynitrite, myoglobin, prostaglandin synthase, PGHS, NO, N2O, O2, CO
National Category
Atom and Molecular Physics and Optics
Identifiers
URN: urn:nbn:se:su:diva-863ISBN: 91-7155-208-1 (print)OAI: oai:DiVA.org:su-863DiVA: diva2:200558
Public defence
2006-03-17, sal FA32, AlbaNova universitetscentrum, Roslagstullsbacken 21, Stockholm, 10:00
Opponent
Supervisors
Available from: 2006-02-20 Created: 2006-02-20Bibliographically approved
List of papers
1. A Theoretical Study on the Binding of O2, NO and CO to Heme Proteins
Open this publication in new window or tab >>A Theoretical Study on the Binding of O2, NO and CO to Heme Proteins
2005 In: Journal of Inorganic Biochemistry, ISSN 0162-0134, Vol. 99, 949-958 p.Article in journal (Refereed) Published
Identifiers
urn:nbn:se:su:diva-25803 (URN)
Note
Part of urn:nbn:se:su:diva-863Available from: 2006-02-20 Created: 2006-02-20Bibliographically approved
2. Theoretical Study of the Energetics of Proton Pumping and Oxygen Reduction in Cytochrome Oxidase
Open this publication in new window or tab >>Theoretical Study of the Energetics of Proton Pumping and Oxygen Reduction in Cytochrome Oxidase
2003 In: Journal of Physical Chemistry B, ISSN 1520-6106, Vol. 107, 10946-10955 p.Article in journal (Refereed) Published
Identifiers
urn:nbn:se:su:diva-25804 (URN)
Note
Part of urn:nbn:se:su:diva-863Available from: 2006-02-20 Created: 2006-02-20Bibliographically approved
3. A Theoretical Study on Nitric Oxide Reductase Activity in a ba3-type Heme-Copper Oxidase
Open this publication in new window or tab >>A Theoretical Study on Nitric Oxide Reductase Activity in a ba3-type Heme-Copper Oxidase
2006 In: Biochimica et Biophysica Acta (BBA) - Bioenergetics, ISSN 0005-2728, Vol. 1757, 31-46 p.Article in journal (Refereed) Published
Identifiers
urn:nbn:se:su:diva-25805 (URN)
Note
Part of urn:nbn:se:su:diva-863Available from: 2006-02-20 Created: 2006-02-20Bibliographically approved
4. Reduction of Nitric Oxide in Bacterial Nitric Oxide Reductase: A Theoretical Model Study
Open this publication in new window or tab >>Reduction of Nitric Oxide in Bacterial Nitric Oxide Reductase: A Theoretical Model Study
2006 (English)In: Biochimica et Biophysica Acta - Bioenergetics, ISSN 0005-2728, E-ISSN 1879-2650, Vol. 1757, no 4, 240-252 p.Article in journal (Refereed) Published
Abstract [en]

The mechanism of the nitric oxide reduction in a bacterial nitric oxide reductase (NOR) has been investigated in two model systems of the heme-b3-FeB active site using density functional theory (B3LYP). A model with an octahedral coordination of the non-heme FeB consisting of three histidines, one glutamate and one water molecule gave an energetically feasible reaction mechanism. A tetrahedral coordination of the non-heme iron, corresponding to the one of CuB in cytochrome oxidase, gave several very high barriers which makes this type of coordination unlikely. The first nitric oxide coordinates to heme b3 and is partly reduced to a more nitroxyl anion character, which activates it toward an attack from the second NO. The product in this reaction step is a hyponitrite dianion coordinating in between the two irons. Cleaving an NO bond in this intermediate forms an FeB (IV)O and nitrous oxide, and this is the rate determining step in the reaction mechanism. In the model with an octahedral coordination of FeB the intrinsic barrier of this step is 16.3 kcal/mol, which is in good agreement with the experimental value of 15.9 kcal/mol. However, the total barrier is 21.3 kcal/mol, mainly due to the endergonic reduction of heme b3 taken from experimental reduction potentials. After nitrous oxide has left the active site the ferrylic FeB will form a μ-oxo bridge to heme b3 in a reaction step exergonic by 45.3 kcal/mol. The formation of a quite stable μ-oxo bridge between heme b3 and FeB is in agreement with this intermediate being the experimentally observed resting state in oxidized NOR. The formation of a ferrylic non-heme FeB in the proposed reaction mechanism could be one reason for having an iron as the non-heme metal ion in NOR instead of a Cu as in cytochrome oxidase.

Keyword
Nitric oxide reductase, NOR, Heme-copper oxidase, Nitrous oxide, Nitric oxide, DFT, B3LYP
National Category
Physical Sciences
Identifiers
urn:nbn:se:su:diva-25806 (URN)10.1016/j.bbabio.2006.04.008 (DOI)
Available from: 2006-02-20 Created: 2006-02-20 Last updated: 2011-02-24Bibliographically approved
5. Theoretical Study of the Reduction of Nitric Oxide in an A-type Flavoprotein
Open this publication in new window or tab >>Theoretical Study of the Reduction of Nitric Oxide in an A-type Flavoprotein
Manuscript (Other academic)
Identifiers
urn:nbn:se:su:diva-25807 (URN)
Note
Part of urn:nbn:se:su:diva-863Available from: 2006-02-20 Created: 2006-02-20 Last updated: 2010-01-13Bibliographically approved
6. A Theoretical Study of Myoglobin Working as a Nitric Oxide Scavenger
Open this publication in new window or tab >>A Theoretical Study of Myoglobin Working as a Nitric Oxide Scavenger
2004 In: Journal of Biological Inorganic Chemistry, ISSN 0949-8257, Vol. 9, 923-935 p.Article in journal (Refereed) Published
Identifiers
urn:nbn:se:su:diva-25808 (URN)
Note
Part of urn:nbn:se:su:diva-863Available from: 2006-02-20 Created: 2006-02-20Bibliographically approved
7. A Quantum Chemical Study of the Synthesis of Prostaglandin G2 by the Cyclooxygenase Active Site in Prostaglandin Endoperoxide H Synthase 1
Open this publication in new window or tab >>A Quantum Chemical Study of the Synthesis of Prostaglandin G2 by the Cyclooxygenase Active Site in Prostaglandin Endoperoxide H Synthase 1
Show others...
2003 In: Journal of Physical Chemistry B, ISSN 1520-6106, Vol. 107, 3297-3308 p.Article in journal (Refereed) Published
Identifiers
urn:nbn:se:su:diva-25809 (URN)
Note
Part of urn:nbn:se:su:diva-863Available from: 2006-02-20 Created: 2006-02-20Bibliographically approved

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