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Titolo:
CRYSTALLOGRAPHIC EVIDENCE FOR THE ACTION OF POTASSIUM, THALLIUM, AND LITHIUM IONS ON FRUCTOSE-1,6-BISPHOSPHATASE
Autore:
VILLERET V; HUANG SH; FROMM HJ; LIPSCOMB WN;
Indirizzi:
HARVARD UNIV,GIBBS CHEM LAB,12 OXFORD ST CAMBRIDGE MA 02138 HARVARD UNIV,GIBBS CHEM LAB CAMBRIDGE MA 02138 IOWA STATE UNIV SCI & TECHNOL,DEPT BIOCHEM & BIOPHYS AMES IA 50011
Titolo Testata:
Proceedings of the National Academy of Sciences of the United Statesof America
fascicolo: 19, volume: 92, anno: 1995,
pagine: 8916 - 8920
SICI:
0027-8424(1995)92:19<8916:CEFTAO>2.0.ZU;2-K
Fonte:
ISI
Lingua:
ENG
Soggetto:
FRUCTOSE 2,6-BISPHOSPHATE; INOSITOL MONOPHOSPHATASE; CRYSTAL-STRUCTURE; NEUTRAL FORM; 6-PHOSPHATE; INHIBITION; RESOLUTION; MECHANISM; 1,6-BISPHOSPHATASE; ACTIVATION;
Keywords:
X-RAY CRYSTALLOGRAPHY; ALLOSTERIC ENZYME; BINDING SITES;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
36
Recensione:
Indirizzi per estratti:
Citazione:
V. Villeret et al., "CRYSTALLOGRAPHIC EVIDENCE FOR THE ACTION OF POTASSIUM, THALLIUM, AND LITHIUM IONS ON FRUCTOSE-1,6-BISPHOSPHATASE", Proceedings of the National Academy of Sciences of the United Statesof America, 92(19), 1995, pp. 8916-8920

Abstract

Fructose-1,6-bisphosphatase (Fru-1,6-Pase; D-fructose-1,6-bisphosphate 1-phosphohydrolase, EC 3.1.3.11) requires two divalent metal ions tohydrolyze alpha-D-fruclose 1,6-bisphosphate. Although not required for catalysis, monovalent cations modify the enzyme activity; K+ and Tlions are activators, whereas Li+ ions are inhibitors. Their mechanisms of action are still unknown. We report here crystallographic structures of pig kidney Fru-1,6-Pase complexed with K+, Tl+, or both Tl+ andLi+. In the T form Fru-1,6-Pase complexed with the substrate analogue2,5-anhydro-D-glucitol 1,6-bisphosphate (AhG-1,6-P-2) and Tl+ or K+ ions, three Tl+ or K+ binding sites are found. Site 1 is defined by Glu-97, Asp-118, Asp-121, Glu-280, and a 1-phosphate oxygen of AhG-1,6-P-2; site 2 is defined by Glu-97, Glu-98, Asp-118, and Leu-120. Finally,site 3 is defined by Arg-276, Glu-280, and the 1-phosphate group of AhG-1,6-P-2. The Tl+ or K+ ions at sites 1 and 2 are very close to the positions previously identified for the divalent metal ions. Site 3 isspecific to K+ or Tl+. In the divalent metal ion complexes, site 3 isoccupied by the guanidinium group of Arg-276. These observations suggest that Tl+ or K+ ions can substitute for Arg-276 in the active site and polarize the 1-phosphate group, thus facilitating nucleophilic attack on the phosphorus center. In the T form complexed with both Tl+ and Li+ ions, Li+ replaces Tl+ at metal site 1. Inhibition by lithium very likely occurs as it binds to this site, thus retarding turnover or phosphate release. The present study provides a structural basis for asimilar mechanism of inhibition for inositol monophosphatase, one of the potential targets of lithium ions in the treatment of manic depression.

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Documento generato il 27/10/20 alle ore 05:04:51