| 1. |
- De Kerpel, Jan O A, et al.
(författare)
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Geometric and Electronic Structure of Co(II)-Substituted Azurin
- 1999
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Ingår i: The Journal of Physical Chemistry Part B. - : American Chemical Society (ACS). - 1520-5207 .- 1520-6106. ; 103:39, s. 8375-8382
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Tidskriftsartikel (refereegranskat)abstract
- The molecular and electronic structures of Co(II)-substituted azurin have been investigated using several realistic models of the metal coordination sphere. The geometry of the models was optimized using the hybrid density functional B3LYP method and compared to the structures obtained for similar Cu(II) models. It is found that Co(II) prefers a distorted tetrahedral structure with four strong bonds to two histidine nitrogens, the cysteine sulphur, and the backbone carbonyl group. This is in contrast to Cu(II), where two weak axial bonds to methionine and the backbone oxygen are found, combined with three strong bonds to the histidines and cysteine in the equatorial plane of a trigonal bipyramidal structure. The optimal structure of the models conforms with experimental crystal data, indicating that the active-site structure in these proteins is determined by the preferences of the metal ion and its ligand and not by protein strain. The electronic structure and spectrum of the Co(imidazole) 2(SH)(SH) 2(HCONH 2) + model have been investigated in detail using multiconfigurational second-order perturbation theory based on a complete active-space wavefunction (CASPT2). Nine ligand-field transitions and six S cys → Co charge-transfer transitions have been calculated, and all experimentally observed absorption bands in the absorption spectrum of Co(II) azurin have been assigned. It is shown that the Co-S cys bond is more ionic than the Cu-S cys bond and that this causes the blue shift and weakening of the charge-transfer states in the spectrum of Co(II)-substituted azurin compared to native copper protein.
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| 2. |
- De Kerpel, Jan O A, et al.
(författare)
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Protein strain in blue copper proteins studied by free energy perturbations
- 1999
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Ingår i: Proteins: Structure, Function and Genetics. - 0887-3585. ; 36:2, s. 157-174
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Tidskriftsartikel (refereegranskat)abstract
- Free energy perturbations have been performed on two blue copper proteins, plastocyanin and nitrite reductase. By changing the copper coordination geometry, force constants, and charges, we have estimated the maximum energy with which the proteins may distort the copper coordination sphere. By comparing this energy with the quantum chemical energy cost for the same perturbation on the isolated copper complex, various hypotheses about protein strain have been tested. The calculations show that the protein can only modify the copper-methionine bond length by a modest amount of energy -- <5 kJ/mol--and they lend no support to the suggestion that the quite appreciable difference in the copper coordination geometry encountered in the two proteins is a result of the proteins enforcing different Cu- methionine bond lengths. On the contrary, this bond is very flexible, and neither the geometry nor the electronic structure change appreciably when the bond length is changed. Moreover, the proteins are rather indifferent to the length of this bond. Instead, the Cu(II) coordination geometries in the two proteins represent two distinct minima on the potential surface of the copper ligand sphere, characterized by different electronic structures, a tetragonal, mainly or-bonded, structure in nitrite reductase and a trigonal, π-bonded, structure in plastocyanin. In vacuum, the structures have almost the same energy, and they are stabilized in the proteins by a combination of geometric and electrostatic interactions. Plastocyanin favors the bond lengths and electrostatics of the trigonal structure, whereas in nitrite reductase, the angles are the main discriminating factor.
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| 3. |
- De Kerpel, Jan O A, et al.
(författare)
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Theoretical study of the structural and spectroscopic properties of stellacyanin
- 1998
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Ingår i: The Journal of Physical Chemistry Part B. - : American Chemical Society (ACS). - 1520-5207 .- 1520-6106. ; 102:23, s. 4638-4647
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Tidskriftsartikel (refereegranskat)abstract
- The electronic spectrum of the azurin Met121Gln mutant, a model of the blue copper protein stellacyanin, has been studied by ab initio multiconfigurational second-order perturbation theory (the CASPT2 method), including the effect of the protein and solvent by point charges. The six lowest electronic transitions have been calculated and assigned with an error of less than 2400 cm-1. The ground-state singly occupied orbital is found to be a predominantly π antibonding orbital involving Cu3d and Scys3pπ. However, it also contains a significant amount (18%) of Cu-Scys σ antibonding character. This σ interaction is responsible for the appearance in the absorption spectrum of a band at 460 nm, with a significantly higher intensity than observed for other, axial, type 1 copper proteins (i.e., plastocyanin or azurin). The π-σ mixing is caused by the axial glutamine ligand binding at a much shorter distance to copper than the corresponding methionine ligand in the normal blue copper proteins. This explains why, based on its spectral properties, stellacyanin is classified among the rhombic type 1 copper proteins, although its structure is clearly trigonal, as it is for the axial proteins. Calculations have also been performed on structures where the glutamine model coordinates to the copper ion via the deprotonated N∈ atom instead of the O∈ atom. However, the resulting transition energies do not resemble the experimental spectrum obtained at normal or elevated pH. Thus, the results do not confirm the suggestion that the coordinating atom of glutamine changes at high pH.
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| 4. |
- Hemmingsen, Lars, et al.
(författare)
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Nuclear quadrupole interactions in cadmium complexes : Semiempirical and ab initio calculations
- 1999
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Ingår i: Zeitschrift fur Naturforschung - Section A Journal of Physical Sciences. - : Walter de Gruyter GmbH. - 0932-0784. ; 54:6-7, s. 422-430
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Tidskriftsartikel (refereegranskat)abstract
- Semiempirical calculations, based on the so-called angular overlap model, have been compared with ab initio methods (MP2) for the calculation of nuclear quadrupole interactions (NQI's) in cadmium complexes with biologically relevant ligands (H2O, OH-, cysteinate, carboxylate, and imidazole). The assumptions on which the semiempirical model is based have been tested and the comparison indicates that: 1) A change in the Cd-ligand bond length by 0.1 Å may change the electric field gradient (EFG) by about 0.2 a. u.. A simple scheme to incorporate such effects in the semiempirical method is suggested. 2) The effect of ligand-ligand interactions is up to about 0.2 a. u. for the largest diagonal element of the EFG tensor for the tested complexes, and such effects can significantly influence the so-called asymmetry parameter. 3) The position of non-coordinating atoms on the ligands can in some cases (e. g. the hydrogen atoms of water) significantly influence the EFG. The combined effect of non-coordinating atoms and ligand-ligand interactions may cause deviations of up to 0.35 a. u. between ab initio and the semiempirical calculations. 4) In the semiempirical model each ligand is characterised by one parameter, the so-called partial nuclear quadrupole interaction. This parameter has been evaluated by ab initio calculations, and agreement was found within about 0.2 a. u. (≈ 40 Mrad/s) for all ligands except imidazole. 5) A change in the coordination number from 2 to 6 may change the partial NQI by about 0.3 a. u.
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| 5. |
- Lindh, Roland, et al.
(författare)
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On the significance of the trigger reaction in the action of the calicheamicin γI 1 anti-cancer drug
- 1997
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Ingår i: Theoretical Chemistry Accounts. - : Springer Science and Business Media LLC. - 1432-881X .- 1432-2234. ; 97:1, s. 203-210
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Tidskriftsartikel (refereegranskat)abstract
- The significance of the so-called trigger reaction in the reaction mechanism of the calicheamicin γI 1 anti-cancer drug has been studied with ab initio quantum chemical methods. The structures of four fragments of calicheamicin γI 1, consisting of either 39 or 41 atoms, have been fully optimized using the Becke-Perdew86 density functional method and the 6-31G* basis sets. The four structures constitute members of an isodesmic reaction for which the reaction energy is a direct measure of the change in activation energy of the Bergman reaction, caused by the structural rearrangements of the preceding trigger reaction. This difference in activation energy has been calculated with density functional theory, using the exchange-correlation functional mentioned above, and with second-order Møller-Plesset perturbation theory (MP2), employing an ANO-type basis set. In both cases a value of 12 kcal/ mol is obtained. The study firmly supports the hypothesis that the significance of the trigger reaction is to saturate a double bond in the vicinity of the enediyne group, which counteracts the formation of the biradical state of the drug. The MP2 computations became feasible by a novel implementation of an integral-direct, distributed-data, parallel MP2 algorithm.
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| 6. |
- Olsson, Mats H M, et al.
(författare)
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On the relative stability of tetragonal and trigonal Cu(II) complexes with relevance to the blue copper proteins
- 1998
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Ingår i: Journal of Biological Inorganic Chemistry. - : Springer Science and Business Media LLC. - 0949-8257 .- 1432-1327. ; 3:2, s. 109-125
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Tidskriftsartikel (refereegranskat)abstract
- The role of the cysteine thiolate ligand for the unusual copper coordination geometry in the blue copper proteins has been studied by comparing the electronic structure, geometry, and energetics of a number of small Cu(II) complexes. The geometries have been optimised with the density functional B3LYP method, and energies have been calculated by multi- configurational second-order perturbation theory (the CASPT2 method). Most small inorganic Cu(II) complexes assume a tetragonal geometry, where four ligands make σ bonds to a Cu 3d orbital. If a ligand lone-pair orbital instead forms a π bond to the copper ion, it formally occupies two ligand positions in a square coordination, and the structure becomes trigonal. Large, soft, and polarisable ligands, such as SH- and SeH-, give rise to covalent copper-ligand bonds and structures close to a tetrahedron, which might be trigonal or tetragonal with approximately the same stability. On the other hand, small and hard ligands, such as NH3, OH2, and OH-, give ionic bonds and flattened tetragonal structures. It is shown that axial type 1 (blue) copper proteins have a trigonal structure with a π bond to the cysteine sulphur atom, whereas rhombic type 1 and type 2 proteins have a tetragonal structure with σ bonds to all strong ligands. The soft cysteine ligand is essential for the stabilisation of a structure that is close to a tetrahedron (either trigonal or tetragonal), which ensures a low reorganisation energy during electron transfer.
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| 7. |
- Olsson, Mats H M, et al.
(författare)
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Quantum chemical calculations of the reorganization energy of blue- copper proteins
- 1998
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Ingår i: Protein Science. - : Wiley. - 0961-8368 .- 1469-896X. ; 7:12, s. 2659-2668
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Tidskriftsartikel (refereegranskat)abstract
- The inner-sphere reorganization energy for several copper complexes related to the active site in blue-copper protein has been calculated with the density functional B3LYP method. The best model of the blue-copper proteins, Cu(Im)2(SCH3)(S(CH'3)2)(0/+), has a self-exchange inner-sphere reorganization energy of 62 kJ/mol, which is at least 120 kJ/mol lower than for Cu(H2O)(+/2+)/4 This lowering of the reorganization energy is caused by the soft ligands in the blue-copper site, especially the cysteine thiolate and the methionine thioether groups. Soft ligands both make the potential surfaces of the complexes flatter and give rise to oxidized structures that are quite close to a tetrahedron (rather than tetragonal). Approximately half of the reorganization energy originates from changes in the copper-ligand bond lengths and half of this contribution comes from the Cu-S(Cys) bond. A tetragonal site, which is present in the rhombic type 1 blue-copper proteins, has a slightly higher (16 kJ/mol) inner-sphere reorganization energy than a trigonal site, present in the axial type I copper proteins. A site with the methionine ligand replaced by an amide group, as in stellacyanin, has an even higher reorganization energy, about 90 kJ/mol.
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| 8. |
- Olsson, Mats H M, et al.
(författare)
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The influence of axial ligands on the reduction potential of blue copper proteins
- 1999
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Ingår i: Journal of Biological Inorganic Chemistry. - : Springer Science and Business Media LLC. - 0949-8257 .- 1432-1327. ; 4:5, s. 654-663
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Tidskriftsartikel (refereegranskat)abstract
- The reduction potentials of blue copper sites vary between 180 and about 1000 mV. It has been suggested that the reason for this variation is that the proteins constrain the distance between the copper ion and its axial ligands to different values. We have tested this suggestion by performing density functional B3LYP calculations on realistic models of the blue copper proteins, including solvent effects by the polarizable continuum method. Constraining the Cu-S(Met) bond length to values between 245 and 310 pm (the range encountered in crystal structures) change the reduction potential by less than 70 mV. Similarly, we have studied five typical blue copper proteins spanning the whole range of reduction potentials: stellacyanin, plastocyanin, azurin, rusticyanin, and ceruloplasmin. These studies included the methionine (or glutamine) ligand as well as the back-bone carbonyl oxygen group that is a ligand in azurin and is found at larger distances in the other proteins. The active-site models of these proteins show a variation in the reduction potential of about 140 mV, i.e., only a minor part of the range observed experimentally (800 mV). Consequently, we can conclude that the axial ligands have a small influence on the reduction potentials of the blue copper proteins. Instead, the large variation in the reduction potentials seems to arise mainly from variations in the solvent accessibility of the copper site and in the orientation of protein dipoles around the copper site.
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| 9. |
- Pierloot, Kristine, et al.
(författare)
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Relation between the structure and spectroscopic properties of blue copper proteins
- 1998
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Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 120:50, s. 13156-13166
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Tidskriftsartikel (refereegranskat)abstract
- The electronic spectra of three rhombic type 1 blue copper proteins, nitrite reductase, pseudoazurin, and cucumber basic protein, have been studied by ab initio multiconfigurational second-order perturbation theory (the CASPT2 method). The six lowest excitations have been calculated and assigned with an error of less than 1800 cm-1. The singly occupied orbital in the ground-state forms a strongly covalent antibond between the copper ion and the thiolate group of the cysteine ligand with a mixture of σ and π character. This is in contrast to the axial type 1 copper protein plastocyanin which has an almost pure Cu-S(Cys) π interaction. The two brightest lines in the absorption spectrum originate from transitions to the corresponding σ (~460 nm) and π (~600 mm) bonding orbitals. The relative intensity of these two lines is determined by the character of the ground- state orbital. It is possible to obtain a structure closely similar to the one found in nitrite reductase by geometry optimizations with the hybrid density functional B3LYP method in vacuum. It is a tetragonal structure with bonds of mainly σ character to the four ligands like normal square-planar Cu(II) complexes, but the cysteine thiolate group donates much charge to the copper ion and thereby makes the structure strongly distorted toward a tetrahedron. Both this structure and a trigonal π-bonded structure, which also can be obtained for all complexes and is an excellent model of plastocyanin, are equilibrium structures (although usually not with the same ligand models). They have virtually the same energy (within ~7 kJ/mol), and the barrier between them is low. Therefore, small differences in the structure and electrostatics of different proteins may lead to stabilization of one or the other of the structures. The results indicate that axial type 1 proteins have a trigonal structure with an almost pure Cu-S(Cys) π bond, whereas rhombic type 1 proteins have tetragonal structures with a significant σ character in this bond. Type 1.5 and 2 copper-cysteinate proteins arise when the tetragonal structure becomes more flattened than in nitrite reductase, probably by the inclusion of stronger (type 1.5) and more (type 2) ligands.
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| 10. |
- Pierloot, Kristine, et al.
(författare)
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Theoretical study of the electronic spectrum of plastocyanin
- 1997
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Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 119:1, s. 218-226
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Tidskriftsartikel (refereegranskat)abstract
- The electronic spectrum of the blue copper protein plastocyanin has been studied by ab initio multiconfigurational second-order perturbation theory (the CASPT2 method). The six lowest electronic transitions have been calculated and assigned with an error of less than 2000 cm-1. The singly occupied orbital in the ground state is Cu 3d-S(Cys) 3pπ antibonding with some N(His) 2pσ character. The bright blue color originates from an electron transfer to this orbital from the corresponding Cu 3d-S(Cys)3pπ bonding orbital. The influence of different ligand models on the spectrum has been thoroughly studied; Cu(imidazole)2(SCH3)(S(CH3)2)+ as a model of CuHis2CysMet is the smallest system that gives converged results.The spectrum is surprisingly sensitive to changes in the geometry, especially in the Cu-S bond distances; a 5 pm change in the Cu-S(Cys) bond length may change the excitation energies by as much as 2000 cm-1. The effect of the surrounding protein and solvent on the transition energies has been modeled by point charges and is found to be significant for some of the transitions (up to 2000 cm-1).
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