1efr: Difference between revisions
No edit summary |
No edit summary |
||
| Line 4: | Line 4: | ||
==Overview== | ==Overview== | ||
In the previously determined structure of mitochondrial F1-ATPase | In the previously determined structure of mitochondrial F1-ATPase determined with crystals grown in the presence of adenylyl-imidodiphosphate (AMP-PNP) and ADP, the three catalytic beta-subunits have different conformations and nucleotide occupancies. AMP-PNP and ADP are bound to subunits beta TP and beta DP, respectively, and the third beta-subunit (beta E) has no bound nucleotide. The efrapeptins are a closely related family of modified linear peptides containing 15 amino acids that inhibit both ATP synthesis and hydrolysis by binding to the F1 catalytic domain of F1F0-ATP synthase. In crystals of F1-ATPase grown in the presence of both nucleotides and inhibitor, efrapeptin is bound to a unique site in the central cavity of the enzyme. Its binding is associated with small structural changes in side chains of F1-ATPase around the binding pocket. Efrapeptin makes hydrophobic contacts with the alpha-helical structure in the gamma-subunit, which traverses the cavity, and with subunit beta E and the two adjacent alpha-subunits. Two intermolecular hydrogen bonds could also form. Intramolecular hydrogen bonds probably help to stabilize efrapeptin's two domains (residues 1-6 and 9-15, respectively), which are connected by a flexible region (beta Ala-7 and Gly-8). Efrapeptin appears to inhibit F1-ATPase by blocking the conversion of subunit beta E to a nucleotide binding conformation, as would be required by an enzyme mechanism involving cyclic interconversion of catalytic sites. | ||
==About this Structure== | ==About this Structure== | ||
| Line 13: | Line 13: | ||
[[Category: Bos taurus]] | [[Category: Bos taurus]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Transferred entry: 3 | [[Category: Transferred entry: 3 6.3 14]] | ||
[[Category: Abrahams, J | [[Category: Abrahams, J P.]] | ||
[[Category: Buchanan, S | [[Category: Buchanan, S K.]] | ||
[[Category: Fearnley, I | [[Category: Fearnley, I M.]] | ||
[[Category: Leslie, A | [[Category: Leslie, A G.W.]] | ||
[[Category: Raaij, M | [[Category: Raaij, M J.Van.]] | ||
[[Category: Walker, J | [[Category: Walker, J E.]] | ||
[[Category: ADP]] | [[Category: ADP]] | ||
[[Category: ANP]] | [[Category: ANP]] | ||
| Line 30: | Line 30: | ||
[[Category: hydrogen ion transport]] | [[Category: hydrogen ion transport]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:27:14 2008'' | ||
Revision as of 13:27, 21 February 2008
|
BOVINE MITOCHONDRIAL F1-ATPASE COMPLEXED WITH THE PEPTIDE ANTIBIOTIC EFRAPEPTIN
OverviewOverview
In the previously determined structure of mitochondrial F1-ATPase determined with crystals grown in the presence of adenylyl-imidodiphosphate (AMP-PNP) and ADP, the three catalytic beta-subunits have different conformations and nucleotide occupancies. AMP-PNP and ADP are bound to subunits beta TP and beta DP, respectively, and the third beta-subunit (beta E) has no bound nucleotide. The efrapeptins are a closely related family of modified linear peptides containing 15 amino acids that inhibit both ATP synthesis and hydrolysis by binding to the F1 catalytic domain of F1F0-ATP synthase. In crystals of F1-ATPase grown in the presence of both nucleotides and inhibitor, efrapeptin is bound to a unique site in the central cavity of the enzyme. Its binding is associated with small structural changes in side chains of F1-ATPase around the binding pocket. Efrapeptin makes hydrophobic contacts with the alpha-helical structure in the gamma-subunit, which traverses the cavity, and with subunit beta E and the two adjacent alpha-subunits. Two intermolecular hydrogen bonds could also form. Intramolecular hydrogen bonds probably help to stabilize efrapeptin's two domains (residues 1-6 and 9-15, respectively), which are connected by a flexible region (beta Ala-7 and Gly-8). Efrapeptin appears to inhibit F1-ATPase by blocking the conversion of subunit beta E to a nucleotide binding conformation, as would be required by an enzyme mechanism involving cyclic interconversion of catalytic sites.
About this StructureAbout this Structure
1EFR is a Protein complex structure of sequences from Bos taurus with , and as ligands. Active as Transferred entry: 3.6.3.14, with EC number 3.6.1.34 Known structural/functional Sites: and . Full crystallographic information is available from OCA.
ReferenceReference
The structure of bovine F1-ATPase complexed with the peptide antibiotic efrapeptin., Abrahams JP, Buchanan SK, Van Raaij MJ, Fearnley IM, Leslie AG, Walker JE, Proc Natl Acad Sci U S A. 1996 Sep 3;93(18):9420-4. PMID:8790345
Page seeded by OCA on Thu Feb 21 12:27:14 2008