Inhibitory sites in enzymes: Zinc removal and reactivation by thionein

被引:327
作者
Maret, W
Jacob, C
Vallee, BL
Fischer, EH
机构
[1] Harvard Univ, Sch Med, Ctr Biochem & Biophys Sci & Med, Boston, MA 02115 USA
[2] Univ Washington, Dept Biochem, Seattle, WA 98195 USA
关键词
D O I
10.1073/pnas.96.5.1936
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Thionein (T) has not been isolated previously from biological material. However, it is generated transiently in situ by removal of zinc from metallothionein under oxidoreductive conditions, particularly in the presence of selenium compounds. T very rapidly activates a group of enzymes in which zinc is bound at an inhibitory site. The reaction is selective, as is apparent from the fact that T does not remove zinc from the catalytic sites of zinc metalloenzymes. T instantaneously reverses the zinc inhibition with a stoichiometry commensurate with its known capacity to bind seven zinc atoms in the form of clusters in metallothionein. The zinc inhibition is much more pronounced than was previously reported, with dissociation constants in the low nanomolar range. Thus, T is an effective, endogenous chelating agent, suggesting the existence of a hitherto unknown and unrecognized biological regulatory system. T removes the metal from an inhibitory zinc-specific enzymatic site with a resultant marked increase of activity. The potential significance of this system is supported by the demonstration of its operations in enzymes involved in glycolysis and signal transduction.
引用
收藏
页码:1936 / 1940
页数:5
相关论文
共 30 条
[1]   Native carboxypeptidase a in a new crystal environment reveals a different conformation of the important tyrosine 248 [J].
Bukrinsky, ET ;
Bjerrum, MJ ;
Kadziola, A .
BIOCHEMISTRY, 1998, 37 (47) :16555-16564
[2]   Differential sensitivity of recombinant N-methyl-D-aspartate receptor subtypes to zinc inhibition [J].
Chen, NS ;
Moshaver, A ;
Raymond, LA .
MOLECULAR PHARMACOLOGY, 1997, 51 (06) :1015-1023
[3]  
CHNG CR, 1998, J TRACE ELEM EXPL ME, V11, P335
[4]  
COLEMAN JE, 1960, J BIOL CHEM, V235, P390
[5]   CDNA ISOLATED FROM A HUMAN T-CELL LIBRARY ENCODES A MEMBER OF THE PROTEIN-TYROSINE-PHOSPHATASE FAMILY [J].
COOL, DE ;
TONKS, NK ;
CHARBONNEAU, H ;
WALSH, KA ;
FISCHER, EH ;
KREBS, EG .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1989, 86 (14) :5257-5261
[6]  
ELLIOTT JI, 1980, J INORG BIOCHEM, V12, P323
[7]   Inhibition of carboxypeptidase A by excess zinc: Analysis of the structural determinants by X-ray crystallography [J].
GomezOrtiz, M ;
GomisRuth, FX ;
Huber, R ;
Aviles, FX .
FEBS LETTERS, 1997, 400 (03) :336-340
[8]   KINETICS OF BINDING OF ZINC(2) BY APOCARBONIC ANHYDRASE [J].
HENKENS, RW ;
STURTEVA.JM .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1968, 90 (10) :2669-&
[9]   Control of zinc transfer between thionein, metallothionein, and zinc proteins [J].
Jacob, C ;
Maret, W ;
Vallee, BL .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (07) :3489-3494
[10]   The glutathione redox couple modulates zinc transfer from metallothionein to zinc-depleted sorbitol dehydrogenase [J].
Jiang, LJ ;
Maret, W ;
Vallee, BL .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (07) :3483-3488