个人简介

B.S., University of Iceland, Reykjavík Ph.D., Colorado State University, Fort Collins

研究领域

Time-resolved spectroscopy, biophysics and bioenergetics, ligand binding and electron transfer dynamics of redox metalloproteins, heme-copper oxidases, proton translocation

The primary aim of my research is to understand the mechanism of coupled electron transfer and proton translocation in cytochrome oxidases. A spectroscopic and kinetics approach on time scales from nanoseconds to milliseconds is emphasized. Our specific focus involves four problems. 1. The mechanism by which dioxygen is reduced to water by cytochrome oxidase remains elusive. We are studying this reaction under a variety of conditions on nanosecond and longer time scales using the flow-flash method, in which the reaction is initiated by photodissociation of the CO complex in the presence of O2. Time-resolved multi-channel optical absorption spectroscopy, in conjunction with singular value decomposition and global exponential fitting analysis, is used to follow the kinetics of electron and proton transfer and to deduce the UV-Vis spectra of the transient intermediates. These studies are providing new insight into the mechanism of the dioxygen reduction by cytochrome oxidase. 2. The reaction of unliganded reduced cytochrome oxidase with oxygen is being investigated using O2 which is produced in situ by photodissociating synthetic dioxygen carriers such as dicobalt μ-peroxo polyamine complexes. This represents a new approach to study the fast dioxygen reactions of cytochrome oxidase and it avoids mechanistic ambiguities associated with the fate of photodissociated CO in traditional flow-flash experiments. This approach will be applied to other oxygen activating systems which are too rapid for conventional stopped-flow techniques or where the flow-flash approach is inapplicable (e.g. non-heme oxidases). 3. The details of the pathways of intramolecular electron transfer (ET) in cytochrome oxidase and the cytochrome c/cytochrome oxidase complex are being studied. We are currently investigating intramolecular ET in cytochrome oxidase using pulse radiolysis. We are also studying intramolecular ET in the electrostatic cytochrome c/cytochrome oxidase complex upon light-induced electron injection from a dye, thiouredo-pyrenetrisulfonate (TUPS), covalently attached to lysine or cysteine residues on cytochrome c. The kinetics are monitored by multichannel detection and the data is analyzed by singular value decomposition and global exponential fitting to elucidate the mechanism and the spectra of the intermediates involved. This approach will be extended to oxidases and cytochrome c from bacteria, where specific amino acids on cytochrome c can be mutated to cysteine and the dye covalently attached. By varying the distance between the labeled cysteine and the heme of the cytochrome c and by introducing breaks into proposed electron transfer pathways, more detailed information regarding intramolecular ET pathways in cytochrome c/cytochrome oxidase can be obtained. 4. The mechanism of the redox-linked proton pump in cytochrome oxidase is unknown. We are investigating the kinetics of electron transfer and proton pumping upon flash-induced oxidation of cytochrome oxidase reconstituted into phospholipid vesicles. The kinetics are being probed by time-resolved optical absorption spectroscopy on time scales from nanoseconds to milliseconds in conjunction with pH indicators located in the extra-vesicular space or covalently bound to the lipids or the protein's extracellular surface. These studies will allow us to correlate proton pumping events with individual steps in the dioxygen reduction cycle and will provide a foundation for a structural model of the energy transduction mechanism in cytochrome oxidase.

近期论文

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Istvan Szundi, Chie Funatogawa, James A. Fee, Tewfik Soulimane, Ólöf Einarsdóttir. CO impedes superfast O2 binding in ba3 cytochrome oxidase from Thermus thermophilus. Proc Natl Acad Sci U S A. 2010 December 7; 107(49): 21010–21015. Published online 2010 November 19. Maximillian E. Mahoney, Allen Oliver, Ólöf EinarsdÓttir, Joseph P. Konopelski. Synthesis of a Cyclic Pentapeptide Mimic of the Active Site His-Tyr Cofactor of Cytochrome c Oxidase. J Org Chem. 2009 November 6; 74(21): 8212–8218. Adam Offenbacher, Kimberley N. White, Indranil Sen, Allen G. Oliver, Joseph P. Konopelski, Bridgette A. Barry, Ólöf Einarsdóttir. A Spectroscopic Investigation of a Tridentate Cu-Complex Mimicking the Tyrosine-Histidine Cross-Link of Cytochrome c Oxidase. J Phys Chem B. 2009 May 21; 113(20): 7407–7417. B. A. Barry and Ó. Einarsdóttir, “Insights into the Structure and Function of Redox-Active Tyrosines from Model Compounds,” J. Phys. Chem. B. (Feature Article) 2005, 109, 6972-6981. I. Szundi, J. Cappuccio, and Ó. Einarsdóttir, “Amplitude Analysis of Single-Wavelength Time-Dependent Absorption Data Does Not Support the conventional Sequential Mechanism for the Reduction of dioxygen to Water Catalyzed by Bovine Heart Cytochrome c Oxidase,” Biochemistry 43, 15746-15758, 2004. Ó. Einarsdóttir and I. Szundi, “Time-Resolved Optical Absorption Studies of Cytochrome Oxidase Dynamics,” Biochim. Biophys. Acta, 2003, 1655, 263, 263-273, 2004. I. Szundi, N. Van Eps, and Ó. Einarsdóttir, “The pH dependence of the Reduction of Dioxygen to Water by Cytochrome c Oxidase. 2. Branched Electron Transfer Pathways Linked by Proton Transfer,” Biochemistry, 42, 5074-5090, 2003. N. Van Eps, I. Szundi and Ó. Einarsdóttir, “The pH dependence of the Reduction of Dioxygen to Water by Cytochrome c Oxidase. 1. The PR State is a pH-dependent Mixture of three Intermediates A, P and F,” Biochemistry, 2003, 42, 5065-5073, 2003. Ó. Einarsdóttir, I. Szundi, N. Van Eps, and A. Sucheta,, “PM and PR forms of Cytochrome c Oxidase have Different Spectral Properties,” J. Inorg. Biochem. 91, 87-93, 2002. J. A. Cappuccio, I. Ayala, Gergory, I. Elliott, I. Szundi, J. Lewis, J. P. Konopelski, B. A. Barry, and Ó. Einarsdóttir, “Modeling the Active Site of Cytochrome Oxidase: Synthesis and Characterization of a Cross-linked Hstidine-Phenol,” J. Am. Chem. Soc.124, 1750-1760, 2002.