1fpk
From Proteopedia
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==Overview== | ==Overview== | ||
| - | 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 to, hydrolyze alpha-D-fructose 1,6-bisphosphate. Although not required for, catalysis, monovalent cations modify the enzyme activity; K+ and Tl+ ions, 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+ and Li+. In, the T form Fru-1,6-Pase complexed with the substrate analogue, 2,5-anhydro-D-glucitol 1,6-bisphosphate (AhG-1,6-P2) 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-P2; site 2, is defined by ... | + | 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 to, hydrolyze alpha-D-fructose 1,6-bisphosphate. Although not required for, catalysis, monovalent cations modify the enzyme activity; K+ and Tl+ ions, 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+ and Li+. In, the T form Fru-1,6-Pase complexed with the substrate analogue, 2,5-anhydro-D-glucitol 1,6-bisphosphate (AhG-1,6-P2) 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-P2; 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-P2. 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 is specific to K+ or Tl+., In the divalent metal ion complexes, site 3 is occupied 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 a similar mechanism of inhibition for inositol, monophosphatase, one of the potential targets of lithium ions in the, treatment of manic depression. |
==About this Structure== | ==About this Structure== | ||
| - | 1FPK is a | + | 1FPK is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa] with TL as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Fructose-bisphosphatase Fructose-bisphosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.11 3.1.3.11] Structure known Active Sites: TH1, TH2, TH3, TH4, TH5 and TH6. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1FPK OCA]. |
==Reference== | ==Reference== | ||
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[[Category: phosphoric monoester]] | [[Category: phosphoric monoester]] | ||
| - | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 5 14:16:25 2007'' |
Revision as of 12:11, 5 November 2007
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FRUCTOSE-1,6-BISPHOSPHATASE (D-FRUCTOSE-1,6-BISPHOSPHATE 1-PHOSPHOHYDROLASE) COMPLEXED WITH THALLIUM IONS (10 MM)
Overview
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 to, hydrolyze alpha-D-fructose 1,6-bisphosphate. Although not required for, catalysis, monovalent cations modify the enzyme activity; K+ and Tl+ ions, 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+ and Li+. In, the T form Fru-1,6-Pase complexed with the substrate analogue, 2,5-anhydro-D-glucitol 1,6-bisphosphate (AhG-1,6-P2) 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-P2; 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-P2. 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 is specific to K+ or Tl+., In the divalent metal ion complexes, site 3 is occupied 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 a similar mechanism of inhibition for inositol, monophosphatase, one of the potential targets of lithium ions in the, treatment of manic depression.
About this Structure
1FPK is a Single protein structure of sequence from Sus scrofa with TL as ligand. Active as Fructose-bisphosphatase, with EC number 3.1.3.11 Structure known Active Sites: TH1, TH2, TH3, TH4, TH5 and TH6. Full crystallographic information is available from OCA.
Reference
Crystallographic evidence for the action of potassium, thallium, and lithium ions on fructose-1,6-bisphosphatase., Villeret V, Huang S, Fromm HJ, Lipscomb WN, Proc Natl Acad Sci U S A. 1995 Sep 12;92(19):8916-20. PMID:7568043
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