Structural and energetic investigations of [Ml(H2O)5]+ by density functional calculations M = Zn2+, Ca2+, and Cd2+; L = His and Glu )

446

Journal of Inorganic Biochemistry

Abstracts

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STRUCTURAL AND ENERGETIC INVESTIGATIONS OF [ML(H20)5] + BY DENSITY FUNCTIONAL CALCULATIONS (M = Zn 2+, Ca 2÷, and Cd2÷; L= His and Glu).

K. Waizumi, a M. Kitajima, a T. Morita, b and N. Fukushima c

a Department of Chemistry, Faculty of Education, Yamaguchi University, Yoshida, Yamaguchi 753, Japan; b Japan Space Utilization Promotion Center, 3-30-16 Nishiwaseda, Shinjuku-ku, Tokyo 169, Japan; c Nihon SiliconGraphics°Cray, 4-20-3 Ebisu Shibuya-ku, Tokyo 150, Japan Insulin is stored as a crystalline array of hexamers in the secretory granules of the pancreatic [3-cells with high concentration of zinc and calcium ions [1]. From a number of diffraction and spectroscopic studies, the His(B10) and Glu(B13) sites of insulin are known to play as high-affinity metal binding sites and the bindings of metal ions such as Zn 2+, Ca 2÷, and Cd 2+ to the specific sites are considered to importantly contribute to the formation and stabilization of the hexamers and crystallines [2]. In this study, we discussed the most stable structures and formation energies of octahedral [ML(H20)5] ÷ (M = Zn 2÷, Ca 2÷, and Cd2+; L = His and Glu) by ab initio density functional methods with reference to the affinities and coordination structures of the metal ions for the binding sites. The geometry optimizations were carried out with the contracted Gaussian-type basis sets (DZVP level) by using the DGauss program in the UniChem 3.0 on the CRAY T90 supercomputer. The initial geometries for [ML(H20)5]÷ were assumed to be an octahedra as shown in Fig. l(a) and Fig. 2(a). Nonlocal corrections for the exchange and correlation energies, proposed by Becke and Perdew, have been applied after the final SCF. The final geometries obtained were illustrated in Fig. 1 and Fig. 2 with the formation energies. Among the histidine complexes, only the Ca 2+ - system released the histidine molecule to afford the [Ca(OH)(H20)4] ÷, which is consistent with the fact that Ca 2÷ ion dose not bind to the His(B10) site of insulin [2]. For the glutamic acid complexes, the Ca 2÷ and Cd 2+ ions were both coordinated to two oxygen atoms of the carboxylate in a bidentate manner whose coordination has been also found at the GIu(B13) in (In)6(Cd2÷)2(Cd2÷) crystal (In = insulin monomer) [2]. In our poster session, the results will be discussed with some experimental data of molecular association and crystal nucleation of insulin. This studies is carried out as a part of "Space Utilization Frontiers Joint Research Projects" promoted by NASUDA. (a)

2319kJ/mol.~..

-.,,

1955 kJ/mol

g ~

Fig. 1 The initial (a) and optimized geometries of [M(His)(H20)5] +. M = Zn 2+ Co), Ca 2+ (c), and Cd2+ (d). (

a

)

~

+

(b)

(c)

1

,,..

(d0)H~/~~

05

Fig. 2 The initial (a) and optimized geometries of [M(GIu)(H20)5] ÷. M = Zn 2÷ (b), Ca2÷ (c), and Cd 2÷ (d). 1. S.L. Howell, M. Tyhurst, H. Duvefelt, A. Andresson, and C. Hellerstrom, CellTissueRes., 188, 107 (1978). 2. C.P. Hill, Z. Dauter, E.J. Dodson, G.G. Dodson, and M.F. Dunn, Biochem.,30, 917 (1991), and refs therein.