The ATP–metallothionein complex

Proceedings of the National Academy of Sciences of the United States of America - Tập 95 Số 16 - Trang 9146-9149 - 1998
Lijuan Jiang1, Wolfgang Maret1, Bert L. Vallée1
1Center for Biochemical and Biophysical Sciences and Medicine, Harvard Medical School, Seeley G. Mudd Building, 250 Longwood Avenue, Boston, MA 02115

Tóm tắt

We have previously shown that glutathione (GSH) and glutathione disulfide interact with metallothionein (MT) and modulate its capacity to donate and transfer zinc. In this paper, we show that ATP also forms a 1:1 complex with MT ( K d = 176 ± 33 μM, pH 7.4) that enhances the transfer of zinc to zinc-depleted sorbitol dehydrogenase, increases the rate of thiol–disulfide interchange with Ellman’s reagent [5,5′-dithiobis (Z-nitrobenzoic acid)], and changes the apparent shape of the protein. GTP produces almost identical effects. The corresponding di- or monophosphates and pyrimidine nucleotides, however, neither bind as strongly as ATP nor enhance zinc transfer. Carbamoylation of MT lysines abolishes ATP binding, indicating that these highly conserved residues are part of the binding site. GSH decreases, whereas glutathione disulfide increases, ATP binding. The interaction of MT with two critical cellular ligands, i.e., GSH and ATP, and ensuing effects on zinc transfer and reactivity suggest that MT is not merely a cellular zinc buffer but, rather, actively participates in zinc distribution. Apparently, when isolated, MT lacks two important effectors that affect its redox behavior and function. The magnitude of the binding constant and the cellular concentration of ATP indicate that in the cell MT could be essentially saturated with ATP at low concentrations of GSH. Both the redox and energy states of the cell seem to control zinc distribution from MT, but their relative contributions require further studies.

Từ khóa


Tài liệu tham khảo

B L Vallee, W Maret Metallothionein III, eds K T Suzuki, N Imura, M Kimura (Birkhäuser, Basel, Switzerland), pp. 1–27 (1993).

10.1073/pnas.94.6.2233

10.1073/pnas.95.7.3478

10.1073/pnas.95.7.3483

10.1073/pnas.95.7.3489

10.1042/bj2940219

A H Robbins, D E McRee, M Williamson, S A Collett, N H Xuong, W F Furey, B C Wang, C D Stout J Mol Biol 221, 1269–1293 (1991).

10.1111/j.1432-1033.1992.tb16882.x

10.1021/bi00062a019

10.1007/978-3-0348-6493-0_1

10.1016/0006-3002(62)90124-5

10.1016/0076-6879(91)05127-H

10.1021/bi00240a036

10.1016/0162-0134(93)80028-8

H Sigel, B Song Metal Ions Biol Syst 32, 135–205 (1996).

10.1016/0076-6879(91)05122-C

10.1073/pnas.91.1.237

10.1016/S0021-9258(19)42605-7

10.1096/fasebj.10.12.8903506

10.1016/S0021-9258(19)74077-0

10.1021/bi00058a001

10.1042/bj2610787

10.1016/0167-4838(89)90245-8

10.1016/S0021-9258(19)36747-X

10.1073/pnas.95.1.358

10.1021/bi00344a062

10.1006/bbrc.1994.1973

10.1006/excr.1996.0146

10.1016/0304-4165(83)90182-4

10.1161/01.RES.75.4.760

S K Krezoski, J Villalobos, C F Shaw, D H Petering Biochem J 255, 483–491 (1998).

10.1016/S0021-9258(19)77815-6

10.1016/0022-2836(88)90644-4

10.1042/bj1930441

10.1021/ic00003a049

Thông tin
Thông tin xuất bản

Proceedings of the National Academy of Sciences of the United States of America

Tập 95 Số 16

9146-9149

Thông tin tác giả