The structure of bovine F1-ATPase complexed with the antibiotic inhibitor aurovertin B.

Content Provider	Semantic Scholar
Author	Raaij, Mark J. Van Abrahams, J. P. Leslie, Andrew G. W. Walker, John E.
Copyright Year	1996
Abstract	In the structure of bovine mitochondrial F1-ATPase that was previously 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. Adenylyl-imidodiphosphate is bound to one beta-subunit (betaTP), ADP is bound to the second (betaDP), and no nucleotide is bound to the third (betaE). Here we show that the uncompetitive inhibitor aurovertin B binds to bovine F1 at two equivalent sites in betaTP and betaE, in a cleft between the nucleotide binding and C-terminal domains. In betaDP, the aurovertin B pocket is incomplete and is inaccessible to the inhibitor. The aurovertin B bound to betaTP interacts with alpha-Glu399 in the adjacent alphaTP subunit, whereas the aurovertin B bound to betaE is too distant from alphaE to make an equivalent interaction. Both sites encompass betaArg-412, which was shown by mutational studies to be involved in binding aurovertin. Except for minor changes around the aurovertin pockets, the structure of bovine F1-ATPase is the same as determined previously. Aurovertin B appears to act by preventing closure of the catalytic interfaces, which is essential for a catalytic mechanism involving cyclic interconversion of catalytic sites.
File Format	PDF HTM / HTML
DOI	10.1073/pnas.93.14.6913
Alternate Webpage(s)	http://www.tau.ac.il/lifesci/courses/membrans/f1%20stucture.pdf
PubMed reference number	8692918
Alternate Webpage(s)	https://doi.org/10.1073/pnas.93.14.6913
Journal	Medline
Volume Number	93
Issue Number	14
Journal	Proceedings of the National Academy of Sciences of the United States of America
Language	English
Access Restriction	Open
Content Type	Text
Resource Type	Article