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Title
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GTPase mechanism of Gproteins from the 1.7-A crystal structure of transducin alpha-GDP-AIF-4.
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Authors
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J.Sondek,
D.G.Lambright,
J.P.Noel,
H.E.Hamm,
P.B.Sigler.
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Ref.
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Nature, 1994,
372,
276-279.
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PubMed id
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Abstract
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Aluminium fluoride (AIF-4) activates members of the heterotrimeric G-protein (G
alpha beta gamma) family by binding to inactive G alpha.GDP near the site
occupied by the gamma-phosphate in G alpha.GTP (ref. 3). Here we describe the
crystal structure of transducin alpha.GDP activated with aluminium fluoride (Gt
alpha.GDP.AIF-4.H2O) at 1.7 A, a resolution sufficient to establish the
coordination geometry of the bound aluminium fluoride as well as the extensive
network of direct and water-mediated interactions that stabilize it. These
observations are derived from three independent representations in the
asymmetric unit, eliminating any chance of drawing conclusions based on
stereochemistry imposed by crystal packing. Surprisingly, aluminium fluoride
activates G alpha.GDP by binding with a geometry resembling a pentavalent
intermediate for GTP hydrolysis. The stabilizing interactions involve not only
residues that interact with the gamma-phosphate in Gt alpha.GTP gamma S, but
also conserved residues for GTPase activity. Thus the Gt alpha.GDP.AIF-4.H2O
structure provides new insight into the mechanism of GTP hydrolysis.
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