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PDBsum entry 2lcd
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Transcription
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PDB id
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2lcd
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References listed in PDB file
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Key reference
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Title
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How azide inhibits ATP hydrolysis by the f-Atpases.
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Authors
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M.W.Bowler,
M.G.Montgomery,
A.G.Leslie,
J.E.Walker.
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Ref.
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Proc Natl Acad Sci U S A, 2006,
103,
8646-8649.
[DOI no: ]
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PubMed id
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Abstract
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In the structure of bovine F1-ATPase determined at 1.95-A resolution with
crystals grown in the presence of ADP, 5'-adenylyl-imidodiphosphate, and azide,
the azide anion interacts with the beta-phosphate of ADP and with residues in
the ADP-binding catalytic subunit, betaDP. It occupies a position between the
catalytically essential amino acids, beta-Lys-162 in the P loop and the
"arginine finger" residue, alpha-Arg-373, similar to the site occupied
by the gamma-phosphate in the ATP-binding subunit, betaTP. Its presence in the
betaDP-subunit tightens the binding of the side chains to the nucleotide,
enhancing its affinity and thereby stabilizing the state with bound ADP. This
mechanism of inhibition appears to be common to many other ATPases, including
ABC transporters, SecA, and DNA topoisomerase IIalpha. It also explains the
stimulatory effect of azide on ATP-sensitive potassium channels by enhancing the
binding of ADP.
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Figure 1.
Fig. 1. The  [DP] catalytic site in
the structure of bovine F[1]-ATPase inhibited with azide. The
view is in stereo. Catalytically important residues are shown
with the difference electron density (F[o] – F[c]) for azide
(green mesh, contoured at 3  ) before its inclusion
in the model.
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Figure 2.
Fig. 2. The interactions of azide with catalytic side
chains in bovine F[1]-ATPase. The two negatively charged outer
nitrogen atoms of azide are hydrogen-bonded to -Lys-162
and  -Arg-373, and the inner
positively charged nitrogen atom forms an ionic interaction with
the oxygen atom of the -phosphate of ADP. The
tight interaction between azide and the side chains prevents the
conversion of the subunit to the open conformation and the
release of ADP.
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