On the role of strain in blue copper proteins

Ryde, Ulf; Olsson, Mats H. M.; Roos, Björn O.; Kerpel, Jan O A De; Pierloot, Kristine

doi:10.1007/s007750000147

Cited by 100 publications

(136 citation statements)

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“…There have been numerous reports and reviews supporting the entatic/rack-induced state hypothesis (7,13,19,20,26,59). On the other hand, theoretical and experimental studies have questioned the role of the protein matrix in defining the geometry of the copper center (21,22,24,25). X-ray studies on the apo form of several cupredoxins, showing no changes in the ligands' conformations upon removal of the copper ion, were considered as experimental evidence of the entatic/rack-induced hypothesis for ET copper proteins (27)(28)(29)(30)(31).…”

Section: Discussionmentioning

confidence: 99%

“…This scenario, known as the entatic/rack-induced state hypothesis, was originally formulated for protein-bound cofactors by Lumry and Eyring in 1954 (16) and then extended to electron transfer metalloproteins by Malmström and Williams in the late 1960s (17,18). This concept has been matter of debate along many years (7,15,(19)(20)(21)(22)(23)(24)(25)(26). In particular, Ryde et al have reported in vacuum quantum calculations suggesting the absence of any strain in the geometry adopted by the copper in the protein framework (21,22).…”

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confidence: 99%

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Flexibility of the metal-binding region in apo-cupredoxins

Zaballa

Abriata

Donaire

et al. 2012

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

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Protein-mediated electron transfer is an essential event in many biochemical processes. Efficient electron transfer requires the reorganization energy of the redox event to be minimized, which is ensured by the presence of rigid donor and acceptor sites. Electron transfer copper sites are present in the ubiquitous cupredoxin fold, able to bind one or two copper ions. The low reorganization energy in these metal centers has been accounted for by assuming that the protein scaffold creates an entatic/rack-induced state, which gives rise to a rigid environment by means of a preformed metal chelating site. However, this notion is incompatible with the need for an exposed metal-binding site and protein-protein interactions enabling metallochaperone-mediated assembly of the copper site. Here we report an NMR study that reveals a high degree of structural heterogeneity in the metal-binding region of the nonmetallated Cu A -binding cupredoxin domain, arising from microsecond to second dynamics that are quenched upon metal binding. We also report similar dynamic features in apo-azurin, a paradigmatic blue copper protein, suggesting a general behavior. These findings reveal that the entatic/rack-induced state, governing the features of the metal center in the copper-loaded protein, does not require a preformed metal-binding site. Instead, metal binding is a major contributor to the rigidity of electron transfer copper centers. These results reconcile the seemingly contradictory requirements of a rigid, occluded center for electron transfer, and an accessible, dynamic site required for in vivo copper uptake.metalloproteins | nuclear magnetic resonance | protein dynamics

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Flexibility of the metal-binding region in apo-cupredoxins

Zaballa

Abriata

Donaire

et al. 2012

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

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“…In addition, there are two weaker ligands from a backbone carbonyl group (covalently connected to one of the His ligands and therefore modelled by CH 3 CONHCH 2 CH 2 -imidazole) and the side chain of a Met residue (modelled by CH 3 SCH 3 ), forming a trigonal bipyramidal geometry. The bond distances to the latter two ligands are strongly affected by the surrounding protein [38], so we constrained them to the distance found in crystal structures [72,73]. We have studied this site in both the reduced Cu + (closed-shell singlets) and the oxidised Cu 2+ states (doublet), and we have measured the strength of hydrogen bonds between a probe water molecule and each of the five ligands, i.e.…”

Section: Azurin Modelsmentioning

confidence: 99%

“…We study how the hydrogen-bond strength depends on the type of metal and its oxidation state, the coordination number, the type of the ligand, other ligands of the metal, and on the nature of the second-sphere hydrogen-bond partner. We study over 60 different complexes, taken mainly from our previous theoretical studies of various metalloproteins [18,19,22,38,39,40,41,42,43,44,45,46,47]. The results provide much insight into how metal coordination affects the geometry and energy of hydrogen bonds to ligating…”

Section: Introductionmentioning

confidence: 99%

How are hydrogen bonds modified by metal binding?

Husberg

Ryde

2013

J Biol Inorg Chem

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How are hydrogen bonds modified by metal binding?Husberg, Charlotte; Ryde, Ulf General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.• Users may download and print one copy of any publication from the public portal for the purpose of private study or research.• You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal Take down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. AbstractWe have used density-functional theory calculations to investigate how the hydrogenbond strength is modified when a ligand is bound to a metal, using over 60 model systems involving six metals and eight ligands frequently encountered in metalloproteins. We study how the hydrogen-bond geometry and energy vary with the nature of metal, the oxidation state, the coordination number, the ligand involved in the hydrogen bond, other first-sphere ligands, and different hydrogen-bond probe molecules. The results show that in general, the hydrogen-bond strength is increased for neutral ligands and decreased for negatively charged ligands. The size of the effect is mainly determined by the net charge of the metal complex and all effects are typically decreased when the model is solvated. In water solution, the hydrogen-bond strength can increase by up to 37 kJ/mol for neutral ligands, and that of negatively charged ligands can both increase (for complexes with a negative net charge) or decrease (for positively charged complexes). If the net charge of the complex does not change, there is normally little difference between different metals or different types of complexes. The only exception is observed for sulphur-containing ligands (Met and Cys) and if the ligand is redox active (e.g. high-valent Fe-O complexes).Key Words: hydrogen bonds, metalloproteins, quantum-mechanical calculations, densityfunctional theory, dispersion correction, solvation. 2 IntroductionHydrogen bonds play an important role in all types of biochemical systems, strongly affecting catalysis, ligand binding, and enzyme function, for example [1]. They have been thoroughly studied by a variety of experimental and theoretical methods [2,3,4,5,6,7,8,9,10,11,12,13,14,15] so that the strengths of the common hydrogen bonds in biological systems are accurately known.However, it is well-known that metal sites affect the properties of bound ligands. For example, the pK a value of water in aqueous metal complexes is reduced from 15.7 for bulk water, to 12.8 for Ca 2+ and to 2.2 for Fe 3+ [16]. Therefore, it is also likely that metal ions also change the strength and structure of hydrogen bonds inv...

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“…These structures have formed the basis for a detailed understanding of the biological function of the proteins by elucidating the interplay between the electronic and geometric structure of the metal site (8,15,(32)(33)(34). However, the geometric structures were all determined in the solid state.…”

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confidence: 99%

Determination of the geometric structure of the metal site in a blue copper protein by paramagnetic NMR

Hansen

Led

2006

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

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The biological function of metalloproteins is closely tied to the geometric and electronic structures of the metal sites. Here, we show that the geometric structure of the metal site of a metalloprotein in solution can be determined from experimentally measured electron-nuclear spin-spin interactions obtained by NMR. Thus, the geometric metal site structure of plastocyanin from Anabaena variabilis was determined by including the paramagnetic relaxation enhancement of protons close to the copper site as restraints in a conventional NMR structure determination, together with the distribution of the unpaired electron onto the ligand atoms. Also, the interproton distances (nuclear Overhauser enhancements) and dihedral angles (scalar nuclear spin-spin couplings) normally used in NMR structure determinations were included as restraints. The structure calculations were carried out with the program X-PLOR and a module that takes into account the specific characteristics of the paramagnetic restraints. A well defined metal site structure was obtained with the structural characteristics of the blue copper site, including a distorted tetrahedral geometry, a short Cu-Cys S ␥ bond, and a long Cu-Met S ␦ bond. Overall, the agreement of the obtained metal site structure of Anabaena variabilis plastocyanin with those of other plastocyanins obtained by x-ray crystallography confirms the reliability of the approach.metal site structure ͉ metalloproteins ͉ paramagnetic nuclear relaxation T he biological function of many metalloproteins stems from the geometric and electronic structures of the metal sites imposed by the protein environment. In the blue copper proteins, such as plastocyanins, amicyanins, and azurins, the geometry of the copper site is unusual as compared with smallmolecule copper complexes (1-15). In particular, the metal sites of blue copper proteins are characterized by a short coppersulfur bond. This unusual geometry is believed to be the main reason for the strong covalency of the metal site (10,16,17) and, thus, responsible for the rapid and long-range electron transfer reactivity (18-22) that characterizes the blue copper proteins. Detailed knowledge of the geometric and electronic metal site structures of the blue copper proteins is, therefore, imperative for understanding the function of the proteins at the molecular level.So far, the geometric structure of the metal site in blue copper proteins (12-14) has been determined primarily by x-ray crystallography and extended x-ray absorption fine structure (3,23,24), whereas the electronic structure of the blue copper site has been determined theoretically from quantum chemical calculations (5, 25-27) and experimentally by x-ray absorption spectroscopy (16, 17), and more recently by nuclear paramagnetic relaxation (28-31). These structures have formed the basis for a detailed understanding of the biological function of the proteins by elucidating the interplay between the electronic and geometric structure of the metal site (8,15,(32)(33)(34). However, the geomet...

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On the role of strain in blue copper proteins

Cited by 100 publications

References 31 publications

Flexibility of the metal-binding region in apo-cupredoxins

Flexibility of the metal-binding region in apo-cupredoxins

How are hydrogen bonds modified by metal binding?

Determination of the geometric structure of the metal site in a blue copper protein by paramagnetic NMR

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