Helix swapping between two α/β barrels: crystal structure of phosphoenolpyruvate mutase with bound Mg2+–oxalate
| Autor: | Yong Jia, Zhong Li, Osnat Herzberg, Kui Huang, Debra Dunaway-Mariano |
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| Rok vydání: | 1999 |
| Předmět: |
Models
Molecular crystal structure Protein Conformation Stereochemistry Dimer education Beta sheet Crystallography X-Ray 010402 general chemistry 01 natural sciences Catalysis Oxalate phosphoenolpyruvate mutase 03 medical and health sciences chemistry.chemical_compound Phosphoenolpyruvate mutase Mutase Tetramer Structural Biology Catalytic Domain Animals Magnesium ion Molecular Biology X-ray crystallography 030304 developmental biology Oxalates 0303 health sciences phosphonates Bivalvia 0104 chemical sciences Crystallography chemistry Phosphotransferases (Phosphomutases) Helix Protein Binding |
| Zdroj: | Structure. 7(5):539-548 |
| ISSN: | 0969-2126 |
| DOI: | 10.1016/s0969-2126(99)80070-7 |
| Popis: | Background: Phosphonate compounds are important secondary metabolites in nature and, when linked to macromolecules in eukaryotes, they might play a role in cell signaling. The first obligatory step in the biosynthesis of phosphonates is the formation of a carbon–phosphorus bond by converting phosphoenolpyruvate (PEP) to phosphonopyruvate (P-pyr), a reaction that is catalyzed by PEP mutase. The PEP mutase functions as a tetramer and requires magnesium ions (Mg 2+ ). Results: The crystal structure of PEP mutase from the mollusk Mytilus edulis , bound to the inhibitor Mg 2+ –oxalate, has been determined using multiwavelength anomalous diffraction, exploiting the selenium absorption edge of a selenomethionine-containing protein. The structure has been refined at 1.8 A resolution. PEP mutase adopts a modified α / β barrel fold, in which the eighth α helix projects away from the α / β barrel instead of packing against the β sheet. A tightly associated dimer is formed, such that the two eighth helices are swapped, each packing against the β sheet of the neighboring molecule. A dimer of dimers further associates into a tetramer. Mg 2+ –oxalate is buried close to the center of the barrel, at the C-terminal ends of the β strands. Conclusions: The tetramer observed in the crystal is likely to be physiologically relevant. Because the Mg 2+ –oxalate is inaccessible to solvent, substrate binding and dissociation might be accompanied by conformational changes. A mechanism involving a phosphoenzyme intermediate is proposed, with Asp58 acting as the nucleophilic entity that accepts and delivers the phosphoryl group. The active-site architecture and the chemistry performed by PEP mutase are different from other α / β -barrel proteins that bind pyruvate or PEP, thus the enzyme might represent a new family of α / β -barrel proteins. |
| Databáze: | OpenAIRE |
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