Orbital interactions, electron delocalization and spin coupling in iron-sulfur clusters

Noodleman, Louis; Peng, Chun; Case, David A.; Mouesca, Jean‐Marie

doi:10.1016/0010-8545(95)07011-l

Cited by 810 publications

(773 citation statements)

References 126 publications

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“…The calculated BS ground state of isolated ½Fe 4 S 4 ðSCH 3 Þ 4 3− at the ZINDO level with an optimized geometry by BS-DFT calculation (28) captures the antiferromagnetic spin structure with two iron sites spin up and two iron sites spin down in agreement with the BS-DFT calculations of ref. 17. The calculated BS highest occupied molecular orbital (HOMO), which contributes most to the electron tunneling, is a combination of Fe-Fe σ* and S-S σ*, in agreement with one of the two spin states coexisting at room temperature (17).…”

supporting

confidence: 56%

“…Fe/S clusters have unique electronic properties due to the antiferromagnetically coupled high-spin iron atoms (16)(17)(18)(19). The main feature of such clusters is the exceptionally high quasi degeneracy of the electronic states, which has its origin in the fivefold degeneracy of the d-orbitals of Fe ions.…”

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confidence: 99%

“…The method is based on the analysis of so-called broken-symmetry (BS) states (17) of the donor and acceptor quasi-continuum "bands" to obtain a dynamically averaged picture.…”

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Electron tunneling in respiratory complex I

Hayashi

Stuchebrukhov

2010

Proc. Natl. Acad. Sci. U.S.A.

119

120

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NADH:ubiquinone oxidoreductase (complex I) plays a central role in the respiratory electron transport chain by coupling the transfer of electrons from NADH to ubiquinone to the creation of the proton gradient across the membrane necessary for ATP synthesis. Here the atomistic details of electronic wiring of all Fe/S clusters in complex I are revealed by using the tunneling current theory and computer simulations; both density functional theory and semiempirical electronic structure methods were used to examine antiferromagnetically coupled spin states and corresponding tunneling wave functions. Distinct electron tunneling pathways between neighboring Fe/S clusters are identified; the pathways primarily consist of two cysteine ligands and one additional key residue. Internal water between protein subunits is identified as an essential mediator enhancing the overall electron transfer rate by almost three orders of magnitude to achieve a physiologically significant value. The identified key residues are further characterized by sensitivity of electron transfer rates to their mutations, examined in simulations, and their conservation among complex I homologues. The unusual electronic structure properties of Fe 4 S 4 clusters in complex I explain their remarkable efficiency of electron transfer.electron transfer in proteins | respiratory chain | iron-sulfur clusters N ADH:ubiquinone oxidoreductase (complex I) is a large L-shaped membrane-bound enzyme involved in cellular respiration that catalyzes the oxidation of NADH and the reduction of ubiquinone in mitochondria and respiring bacteria (1-3). This reaction involves the transfer of electrons over approximately 90 Å from NADH bound to the hydrophilic domain to ubiquinone in or near the hydrophobic membrane-bound domain of complex I (4). In turn, the reaction provides the driving force for translocation of four protons across the membrane, thus generating, in part, the proton gradient necessary for ATP synthesis (5). Complex I defects are the cause of several neurodegenerative diseases including Parkinson disease, Alzheimer's disease, and Huntington disease (6).The transfer of electrons from NADH to ubiquinone is facilitated by flavin mononucleotide (FMN), two binuclear (2Fe-2S) iron-sulfur clusters (N1a and N1b), and six tetranuclear (4Fe-4S) iron-sulfur clusters (N3, N4, N5, N6a, N6b, and N2) (Fig. 1A). NADH, a two-electron donor, initially passes both electrons, as hydride, to the FMN cofactor. From FMN one electron enters a transport chain leading to the ubiquinone-binding site; the second electron enters a side path to N1a that appears to serve as a control mechanism to prevent generation of superoxide ions (4).The crystal structure of hydrophilic domain of complex I from Thermus thermophilus was reported in 2006 (4), and recently the whole architecture of the enzyme has been revealed (7); however, until now, the atomistic details of electron transfer along the chain of Fe/S metal clusters have remained unknown. Recently, a hopping (stepwise) electron transfer (...

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Electron tunneling in respiratory complex I

Hayashi

Stuchebrukhov

2010

Proc. Natl. Acad. Sci. U.S.A.

119

120

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“…Mössbauer spectroscopy (24) and theoretical studies (15) have indicated that 4Fe clusters contain delocalized valence electrons distributed over an Fe 2þ -Fe 2þ pair (k 3 ¼ k 4 ) and a mixed valence Fe 2.5þ -Fe 2.5þ pair (k 1 ¼ k 2 ) (see Fig. 6).…”

Section: Spin Projection Factors (Spfs) and G-axis Orientation Combinmentioning

confidence: 99%

“…DEER uses the electron-electron dipolar interaction between two paramagnetic centers to ascertain their separation and relative orientation; it is well established for determining the distances between organic radicals (such as NO • ) with S ¼ 1∕2 ground states and precisely known magnetic moments (12,13). In contrast, applying DEER to metal sites in multicentered enzymes is a relatively new application that builds on the seminal work of Bertrand (14) and Noodleman et al (15) on FeS clusters, and on the application of DEER to a [NiFe]-hydrogenase by Bittl and coworkers (16,17). First, the magnetic moment of a cluster results from ferromagnetic and antiferromagnetic coupling between the Fe subsites and varies with the cluster type and environment (14).…”

mentioning

confidence: 99%

Direct assignment of EPR spectra to structurally defined iron-sulfur clusters in complex I by double electron–electron resonance

Roessler

King

Robinson

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

119

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In oxidative phosphorylation, complex I (NADH:quinone oxidoreductase) couples electron transfer to proton translocation across an energy-transducing membrane. Complex I contains a flavin mononucleotide to oxidize NADH, and an unusually long series of iron-sulfur (FeS) clusters, in several subunits, to transfer the electrons to quinone. Understanding coupled electron transfer in complex I requires a detailed knowledge of the properties of individual clusters and of the cluster ensemble, and so it requires the correlation of spectroscopic and structural data: This has proved a challenging task. EPR studies on complex I from Bos taurus have established that EPR signals N1b, N2 and N3 arise, respectively, from the 2Fe cluster in the 75 kDa subunit, and from 4Fe clusters in the PSST and 51 kDa subunits (positions 2, 7, and 1 along the seven-cluster chain extending from the flavin). The other clusters have either evaded detection or definitive signal assignments have not been established. Here, we combine double electron-electron resonance (DEER) spectroscopy on B. taurus complex I with the structure of the hydrophilic domain of Thermus thermophilus complex I. By considering the magnetic moments of the clusters and the orientation selectivity of the DEER experiment explicitly, signal N4 is assigned to the first 4Fe cluster in the TYKY subunit (position 5), and N5 to the all-cysteine ligated 4Fe cluster in the 75 kDa subunit (position 3). The implications of our assignment for the mechanisms of electron transfer and energy transduction by complex I are discussed.C omplex I (NADH:quinone oxidoreductase) is an essential respiratory enzyme. It is an entry point to the electrontransport chains of many aerobic organisms, and its dysfunction is linked to numerous human diseases by mitochondrial DNA mutations, decreased respiratory capacity and increased oxidative stress (1). Complex I is a complicated, membrane-bound enzyme that couples NADH oxidation and quinone reduction to proton translocation across an energy-transducing membrane. It comprises a membrane extrinsic (hydrophilic) domain, and a membrane intrinsic (hydrophobic) domain. A chain of iron-sulfur (FeS) clusters in the hydrophilic domain is essential in transferring electrons from the flavin mononucleotide at the site of NADH oxidation to the hydrophobic site of quinone reduction. The mechanism by which electron transfer drives proton translocation is not known. The 3.3 Å structure of the hydrophilic domain of Thermus thermophilus complex I, the only high resolution structure available, reveals how the FeS clusters and the flavin are arranged (2). Seven clusters form an extensive chain from the flavin to the quinone binding site; the eighth cluster, of unknown function, is on the opposite side of the flavin (see Fig. 1). A ninth cluster, more than 20 Å from the cluster chain, occurs in only a few species, including T. thermophilus and Escherichia coli. Current knowledge of the properties of the clusters, most obviously their reduction potentials, has been derived ...

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