Yliopiston etusivulle Suomeksi På svenska In English Helsingin yliopisto

A quantum chemical investigation of the metal centres in cytochrome c oxidase

Show full item record

Files in this item

Files Description Size Format View/Open
aquantum.pdf 893.5Kb PDF View/Open
Use this URL to link or cite this item: http://urn.fi/URN:ISBN:978-952-10-3840-2
Vie RefWorksiin
Title: A quantum chemical investigation of the metal centres in cytochrome c oxidase
Author: Johansson, Mikael
Contributor: University of Helsinki, Faculty of Science, Department of Chemistry
Thesis level: Doctoral dissertation (article-based)
Abstract: Quantum effects are often of key importance for the function of biological systems at molecular level. Cellular respiration, where energy is extracted from the reduction of molecular oxygen to water, is no exception. In this work, the end station of the electron transport chain in mitochondria, cytochrome c oxidase, is investigated using quantum chemical methodology.

Cytochrome c oxidase contains two haems, haem a and haem a3. Haem a3, with its copper companion, CuB, is involved in the final reduction of oxygen into water. This binuclear centre receives the necessary electrons from haem a. Haem a, in turn, receives its electrons from a copper ion pair in the vicinity, called CuA.

Density functional theory (DFT) has been used to clarify the charge and spin distributions of haem a, as well as changes in these during redox activity. Upon reduction, the added electron is shown to be evenly distributed over the entire haem structure, important for the accommodation of the prosthetic group within the protein. At the same time, the spin distribution of the open-shell oxidised state is more localised to the central iron. The exact spin density distribution has been disputed in the literature, however, different experiments indicating different distributions of the unpaired electron. The apparent contradiction is shown to be due to the false assumption of a unit amount of unpaired electron density; in fact, the oxidised state has about 1.3 unpaired electrons. The validity of the DFT results have been corroborated by wave function based coupled cluster calculations.

Point charges, for use in classical force field based simulations, have been parameterised for the four metal centres, using a newly developed methodology. In the procedure, the subsystem for which point charges are to be obtained, is surrounded by an outer region, with the purpose of stabilising the inner region, both electronically and structurally.

Finally, the possibility of vibrational promotion of the electron transfer step between haem a and a3 has been investigated. Calculating the full vibrational spectra, at DFT level, of a combined model of the two haems, revealed several normal modes that do shift electron density between the haems. The magnitude of the shift was found to be moderate, at most. The proposed mechanism could have an assisting role in the electron transfer, which still seems to be dominated by electron tunnelling.Kvantmekaniska effekter spelar ofta en avgörande roll för funktionen av biologiska system på molekylär nivå. Cellandingen, där syret vi andas in förbrukas i en energiproducerande reaktion med vatten som produkt, utgör inget undantag. Detta arbete koncenterar sig på ett speciellt enzym, d.v.s. protein, som tar del i denna detaljerade och involverade biokemiska process: cytokrom c oxidas.

Cytokrom c oxidas innehåller flera centra där metallatomer, eller joner, spelar en viktig funktionell roll. Av speciellt intresse här är två hämmolekyler, som innehåller varsin järnatom (analogt med det syretransporterande proteinet hemoglobin), samt två centra som innehåller kopparatomer.

Flera viktiga egenskaper hos dessa metallcentra styrs av kvantmekaniken. I detta arbete har bl.a. laddningsfördelningen hos hämen studerats, samt den till laddningen löst kopplade, helt kvantmekaniska egenskapen elektronens spinn. Kvantkemiska beräkningar förenar två till synes motstridiga experimentella slutsatser om var elektronens spinn befinner sig. Möjligen lite kontraintuitivt, visade det sig att antalet oparade elektroner i ett hämsystem inte är ett heltal; det finns t.ex. 1,3 oparade elektroner i ett av systemen. För en god förståelse av processerna i levande organismer behövs ett nära samarbete mellan experimentalister och teoretiker.

Kvantkemiska beräkningar har också användts för att producera parametrar för enklare beräkningsmetoder baserade på klassisk Newton-mekanik. Med hjälp av dessa kan de biokemiska processerna studeras med en mycket lättare börda för superdatorerna.

En ny mekanism för förflyttningen av elektroner inne i enzymet har också föreslagits och studerats. Möjligen kan denna mekanism hjälpa till eller effektivera elektrontransporten mellan de två hämgrupperna, som dock fortfarande verkar vara dominerad av en annan kvantmekanisk effekt, tunnling.
URI: URN:ISBN:978-952-10-3840-2
Date: 2007-04-13
Copyright information: This publication is copyrighted. You may download, display and print it for Your own personal use. Commercial use is prohibited.
This item appears in the following Collection(s)

Show full item record

Search Helda

Advanced Search


My Account