Document Detail

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>
MedLine Citation:
PMID:  22243519     Owner:  NLM     Status:  Publisher    
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.
David John Blum; Young H Ko; Peter Lynn Pedersen
Related Documents :
12750019 - The design of potent, non-peptidic inhibitors of hepatitis c protease.
22260689 - The regulatory role of the juxtamembrane region in the activity of the epidermal growth...
20620059 - Enhanced selectivity profile of pyrazole-urea based dfg-out p38alpha inhibitors.
22511879 - Dissection of pol ii trigger loop function and pol ii activity-dependent control of sta...
17855089 - Amino(methyl) pyrrolidines as novel scaffolds for factor xa inhibitors.
22781759 - The yeast regulator of transcription protein rtr1 lacks an active site and phosphatase ...
11151009 - Modeling, mutagenesis, and structural studies on the fully conserved phosphate-binding ...
19846069 - Macoma birmanica agglutinin recognizes glycoside clusters of beta-glcnac/glc and alpha-...
12856889 - Arg-72 of pharaonis phoborhodopsin (sensory rhodopsin ii) is important for the maintena...
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-12-22
Journal Detail:
Title:  Biochemistry     Volume:  -     ISSN:  1520-4995     ISO Abbreviation:  -     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2012-1-16     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0370623     Medline TA:  Biochemistry     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Carrageenan induced phosphorylation of Akt is dependent on neurokinin-1 expressing neurons in the su...
Next Document:  Impedance nadir values correlate with barium bolus amount.