Visualizing the enzyme mechanism of mevalonate diphosphate decarboxylase
| Autor: | Cynthia V. Stauffacher, Lake N. Paul, James C. Mermoud, Calvin Steussy, Chun-Liang Chen |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Models
Molecular 0301 basic medicine Carboxy-Lyases Decarboxylation Stereochemistry Science Lysine General Physics and Astronomy 02 engineering and technology Crystallography X-Ray Ligands behavioral disciplines and activities Protein Structure Secondary Article General Biochemistry Genetics and Molecular Biology Substrate Specificity 03 medical and health sciences Protein structure mental disorders Enterococcus faecalis Amino Acid Sequence Binding site lcsh:Science Conserved Sequence X-ray crystallography chemistry.chemical_classification Binding Sites Multidisciplinary biology Active site Substrate (chemistry) General Chemistry Molecular biophysics 021001 nanoscience & nanotechnology 030104 developmental biology Enzyme chemistry Metals Enzyme mechanisms Biocatalysis biology.protein lcsh:Q Mevalonate pathway 0210 nano-technology |
| Zdroj: | Nature Communications, Vol 11, Iss 1, Pp 1-13 (2020) Nature Communications |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/s41467-020-17733-0 |
| Popis: | Mevalonate diphosphate decarboxylases (MDDs) catalyze the ATP-dependent-Mg2+-decarboxylation of mevalonate-5-diphosphate (MVAPP) to produce isopentenyl diphosphate (IPP), which is essential in both eukaryotes and prokaryotes for polyisoprenoid synthesis. The substrates, MVAPP and ATP, have been shown to bind sequentially to MDD. Here we report crystals in which the enzyme remains active, allowing the visualization of conformational changes in Enterococcus faecalis MDD that describe sequential steps in an induced fit enzymatic reaction. Initial binding of MVAPP modulates the ATP binding pocket with a large loop movement. Upon ATP binding, a phosphate binding loop bends over the active site to recognize ATP and bring the molecules to their catalytically favored configuration. Positioned substrates then can chelate two Mg2+ ions for the two steps of the reaction. Closure of the active site entrance brings a conserved lysine to trigger dissociative phosphoryl transfer of γ-phosphate from ATP to MVAPP, followed by the production of IPP. Mevalonate diphosphate decarboxylase (MDD) is a key enzyme in the mevalonate pathway and catalyses the decarboxylation of mevalonate-5-diphosphate to isopentenyl diphosphate. Here, the authors provide insights into the conformational changes that occur during substrate binding of MDD and the subsequent enzymatic reaction steps by determining the substrate and intermediate bound crystal structures of Enterococcus faecalis MDD. |
| Databáze: | OpenAIRE |
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