| Mitochondrial ATP Synthase Catalytic Mechanism: A Novel Visual Comparative Structural Approach Emphasizes Pivotal Roles for Mg<sup>2+</sup> and P-Loop Residues in Making ATP</sup></sup> | |
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MedLine Citation:
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PMID: 22243519 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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The mitochondrial ATP Synthase (FoF1) is one of the most abundant, important, and complex enzymes found in animals and humans. In earlier studies we used the photosensitive phosphate analog vanadate (Vi) to study the enzyme's mechanism in the transition state. Significantly, these studies showed that Mg<sup>2+</sup> plays an important role in transition state formation during ATP synthesis. Additionally, in both MgADP∙Vi-F1 and MgVi-F1 complexes, photoactivation of orthovanadate (Vi) induced cleavage at the third residue within the P-loop (GGAGVGKT), i.e. βA158, suggesting its close proximity to the γ-phosphate during transition state formation. However, despite our recent release of the F1-ATPase structure at 3.0 Å containing Vi, the structural details regarding the role of Mg<sup>2+</sup> have remained elusive. Therefore, in this study, we sought to better understand the essential role of Mg<sup>2+</sup> during transition state formation. We utilized PDB structural data representing different conformational intermers of key steps in ATP synthesis to assemble a database of positional relationships between landmark residues of the catalytic site and bound ligand. Applying novel bioinformatics methods, we combined the resulting interatomic spatial data with an animated model of the catalytic site in order to visualize the exact nature of changes in these positional relationships during ATP synthesis. The results of these studies reported here show that the absence of Mg<sup>2+</sup> results in migration of inorganic phosphate (Pi) away from βA158 to a more medial position in the P-loop binding pocket, thereby disrupting essential placement and orientation of the Pi needed to form the transition state structure and therefore MgATP. |
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Authors:
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David John Blum; Young H Ko; Peter Lynn Pedersen |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-12-22 |
Journal Detail:
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Title: Biochemistry Volume: - ISSN: 1520-4995 ISO Abbreviation: - Publication Date: 2011 Dec |
Date Detail:
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Created Date: 2012-1-16 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0370623 Medline TA: Biochemistry Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
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