The active-site metal coordination geometry of cadmium-substituted alcohol dehydrogenase: A theoretical interpretation of perturbed angular correlation of γ-ray measurements

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T1 - The active-site metal coordination geometry of cadmium-substituted alcohol dehydrogenase

T2 - A theoretical interpretation of perturbed angular correlation of γ-ray measurements

AU - Ryde, U.

AU - Hemmingsen, L.

PY - 1997/10

Y1 - 1997/10

N2 - The structure of eleven complexes of cadmium-substituted alcohol dehydrogenase with or without coenzyme and with different non-protein cadmium ligands has been estimated by combined quantum chemical and molecular mechanical geometry optimisations. The geometry of the optimised complexes is similar to the crystal structure of cadmium-substituted alcohol dehydrogenase, indicating that the method behaves well. The optimised structures do not differ significantly (except for the metal bond lengths) from those of the corresponding zinc complexes, which shows that cadmium is a good probe of zinc coordination geometries. The electric field gradients at the cadmium nucleus have been calculated quantum chemically at the MP2 level with a large cadmium basis set, and they have been used to interpret experimental data obtained by perturbed angular correlation of γ-rays. The experimental and calculated field gradients (all three eigenvalues) differ by less than 0.35 a.u. (3.4·1021 Vm-2), the average error is 0.11 a.u., and the average relative error in the two largest eigenvalues of the field gradients is 9%. Calculated field gradients of four-coordinate structures agree better with the experimental results than do those of any five- coordinate model. Thus, the results indicate that the catalytic metal ion remains four-coordinate in all examined complexes. Two measurements are best explained by a four-coordinate cadmium ion with Glu-68 as the fourth ligand, indicating that Glu-68 probably coordinates intermittently to the catalytic metal ion in horse liver alcohol dehydrogenase under physiological conditions.

AB - The structure of eleven complexes of cadmium-substituted alcohol dehydrogenase with or without coenzyme and with different non-protein cadmium ligands has been estimated by combined quantum chemical and molecular mechanical geometry optimisations. The geometry of the optimised complexes is similar to the crystal structure of cadmium-substituted alcohol dehydrogenase, indicating that the method behaves well. The optimised structures do not differ significantly (except for the metal bond lengths) from those of the corresponding zinc complexes, which shows that cadmium is a good probe of zinc coordination geometries. The electric field gradients at the cadmium nucleus have been calculated quantum chemically at the MP2 level with a large cadmium basis set, and they have been used to interpret experimental data obtained by perturbed angular correlation of γ-rays. The experimental and calculated field gradients (all three eigenvalues) differ by less than 0.35 a.u. (3.4·1021 Vm-2), the average error is 0.11 a.u., and the average relative error in the two largest eigenvalues of the field gradients is 9%. Calculated field gradients of four-coordinate structures agree better with the experimental results than do those of any five- coordinate model. Thus, the results indicate that the catalytic metal ion remains four-coordinate in all examined complexes. Two measurements are best explained by a four-coordinate cadmium ion with Glu-68 as the fourth ligand, indicating that Glu-68 probably coordinates intermittently to the catalytic metal ion in horse liver alcohol dehydrogenase under physiological conditions.

KW - Combined quantum chemical and molecular mechanical geometry optimisation

KW - Electric field gradient

KW - Five-coordination

KW - Nuclear quadrupole interaction

KW - Protein strain

UR - http://www.scopus.com/inward/record.url?scp=0030856130&partnerID=8YFLogxK

U2 - 10.1007/s007750050171

DO - 10.1007/s007750050171

M3 - Article

AN - SCOPUS:0030856130

VL - 2

SP - 567

EP - 579

JO - Journal of Biological Inorganic Chemistry

JF - Journal of Biological Inorganic Chemistry

SN - 1432-1327

IS - 5

ER -