Structural Basis for Morpheein-type Allosteric Regulation of Escherichia coli Glucosamine-6-phosphate Synthase: EQUILIBRIUM BETWEEN INACTIVE HEXAMER AND ACTIVE DIMER
| العنوان: | Structural Basis for Morpheein-type Allosteric Regulation of Escherichia coli Glucosamine-6-phosphate Synthase: EQUILIBRIUM BETWEEN INACTIVE HEXAMER AND ACTIVE DIMER |
|---|---|
| المؤلفون: | Mouilleron, Stéphane, Badet-Denisot, Marie-Ange, Pecqueur, Ludovic, Madiona, Karine, Assrir, Nadine, Badet, Bernard, Golinelli-Pimpaneau, Béatrice |
| المساهمون: | Institut de Chimie des Substances Naturelles (ICSN), Centre National de la Recherche Scientifique (CNRS) |
| المصدر: | Journal of Biological Chemistry Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2012, 287 (41), pp.34533-46. ⟨10.1074/jbc.M112.380378⟩ |
| بيانات النشر: | HAL CCSD, 2012. |
| سنة النشر: | 2012 |
| مصطلحات موضوعية: | Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing), Models, Molecular, Structure-Activity Relationship, Allosteric Regulation, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Escherichia coli Proteins, Enzyme Stability, Escherichia coli, Enzymology, Protein Multimerization, Protein Structure, Quaternary |
| الوصف: | International audience; The amino-terminal cysteine of glucosamine-6-phosphate synthase (GlmS) acts as a nucleophile to release and transfer ammonia from glutamine to fructose 6-phosphate through a channel. The crystal structure of the C1A mutant of Escherichia coli GlmS, solved at 2.5 Å resolution, is organized as a hexamer, where the glutaminase domains adopt an inactive conformation. Although the wild-type enzyme is active as a dimer, size exclusion chromatography, dynamic and quasi-elastic light scattering, native polyacrylamide gel electrophoresis, and ultracentrifugation data show that the dimer is in equilibrium with a hexameric state, in vitro and in cellulo. The previously determined structures of the wild-type enzyme, alone or in complex with glucosamine 6-phosphate, are also consistent with a hexameric assembly that is catalytically inactive because the ammonia channel is not formed. The shift of the equilibrium toward the hexameric form in the presence of cyclic glucosamine 6-phosphate, together with the decrease of the specific activity with increasing enzyme concentration, strongly supports product inhibition through hexamer stabilization. Altogether, our data allow us to propose a morpheein model, in which the active dimer can rearrange into a transiently stable form, which has the propensity to form an inactive hexamer. This would account for a physiologically relevant allosteric regulation of E. coli GlmS. Finally, in addition to cyclic glucose 6-phosphate bound at the active site, the hexameric organization of E. coli GlmS enables the binding of another linear sugar molecule. Targeting this sugar-binding site to stabilize the inactive hexameric state is therefore suggested for the development of specific antibacterial inhibitors. |
| اللغة: | English |
| تدمد: | 0021-9258 1083-351X |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=pmid_dedup__::33d919394f32c081c78dbb304287e7a1 https://hal.archives-ouvertes.fr/hal-00742454 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.pmid.dedup....33d919394f32c081c78dbb304287e7a1 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 00219258 1083351X |
|---|