Metallothionein naturally binds seven gram atoms of divalent ions such as Zn and Cd through cysteines forming two metals binding clusters, each constitutes a domain. Four of the metals [M1, M5, M6, M7] are found in alpha, the C-terminal domain, and three [M2, M3, M4] in beta, the N-terminal domain. The level of avidity is site specific. By semiempirical MNDO calculations, we find the relative binding stability for Cd to be M4 > M2 > M3 in the beta-cluster and M5 > M7 > M1,M6 in the alpha-cluster. This is reflected by energy differences computed with a series of simulated structures derived from either X-ray crystallography or NMR coordinates, Thus, replacement of Zn by Cd can be expected to follow the order: M4 --> M2 --> M3 in the beta-domain and M5 --> M7 --> M1 or M6 in the alpha-domain. Bridging cysteines are stronger than terminal cysteines in their relative average binding strength. Among the terminal cysteines, the strongest binding strength is found in Cys 21 to Cd[M4] and in Cys 26 to Zn[M3], both in the beta-domain of metallothionein. Although the binding strength of cysteine in the alpha domain has not yet been determined, we are able to predict from this study differential contribution of individual cysteines to metal binding. Such a prediction can be further tested by experiments with site-directed mutagenesis.
|發行者||BIRKHAUSER VERLAG AG|
|出版狀態||Published - 1月 1999|
|事件||4TH International Metallothionein Meeting (MT-97) - KANSAS CITY, Macao|
持續時間: 1 1月 1997 → …
|Conference||4TH International Metallothionein Meeting (MT-97)|
|期間||1/01/97 → …|