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Sprang SR. G protein mechanisms: insights from structural analysis. Annu Rev Biochem. 66:1997;639-678.
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Sprang, S.R.1
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Crystal structure of a small G protein in complex with the GTPase-activating protein rhoGAP
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of special interest. In this G protein GAP complex, the G protein, CDC42Hs is stabilized in the enzyme-substrate ground state. Although p50rhoGAP presents a potentially catalytic arginine residue to the catalytic site, this residue does not contact the nucleotide itself, suggesting that a conformational change is required to achieve the active G protein GAP complex.
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Rittinger K, Walker PA, Eccleston JF, Nurmahomed K, Owen D, Laue E, Gamblin SJ, Smerdon SJ. Crystal structure of a small G protein in complex with the GTPase-activating protein rhoGAP. of special interest Nature. 388:1997;693-697 In this G protein GAP complex, the G protein, CDC42Hs is stabilized in the enzyme-substrate ground state. Although p50rhoGAP presents a potentially catalytic arginine residue to the catalytic site, this residue does not contact the nucleotide itself, suggesting that a conformational change is required to achieve the active G protein GAP complex.
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Nature
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Rittinger, K.1
Walker, P.A.2
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Gamblin, S.J.7
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8
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The crystal structure of human rac1, a member of the rho-family complexed with a GTP analogue
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Hirshberg M, Stockley RW, Dodson G, Webb MR. The crystal structure of human rac1, a member of the rho-family complexed with a GTP analogue. Nat Struct Biol. 4:1997;147-152.
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Nat Struct Biol
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Hirshberg, M.1
Stockley, R.W.2
Dodson, G.3
Webb, M.R.4
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9
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Structure of the conserved GTPase domain of the signal recognition particle
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of special interest. These two papers [9, 10] describe the G protein domains of the SRP and SR proteins. While the Ras-like core is preserved in these homologous proteins, it is preceded by a four-helix bundle and is interrupted after the effector loop by a lengthy insertion that adds a seventh strand to the core β sheet. Neither protein contains a nucleotide bound to the active site but, whereas that of Fft is closed, that of FtsY is open. In vivo, these two subunits would dimerize, and each stimulated the GTPase activity of the other.
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Freymann DM, Keenan RJ, Stroud RM, Walter P. Structure of the conserved GTPase domain of the signal recognition particle. of special interest Nature. 385:1997;361-364 These two papers [9, 10] describe the G protein domains of the SRP and SR proteins. While the Ras-like core is preserved in these homologous proteins, it is preceded by a four-helix bundle and is interrupted after the effector loop by a lengthy insertion that adds a seventh strand to the core β sheet. Neither protein contains a nucleotide bound to the active site but, whereas that of Fft is closed, that of FtsY is open. In vivo, these two subunits would dimerize, and each stimulated the GTPase activity of the other.
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Nature
, vol.385
, pp. 361-364
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Freymann, D.M.1
Keenan, R.J.2
Stroud, R.M.3
Walter, P.4
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10
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Crystal structure of the NG domain from the signal-recognition particle receptor FtsY
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of special interest. See annotation [9].
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Montoya G, Svensson C, Luirink J, Sinning I. Crystal structure of the NG domain from the signal-recognition particle receptor FtsY. of special interest Nature. 385:1997;365-368 See annotation [9].
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Nature
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Montoya, G.1
Svensson, C.2
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Sinning, I.4
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Wei Y, Zhang Y, Liu X, Minor W, Nakamoto RK, Somlyo AV, Somlyo AP, Derewenda ZS. Crystal structure of RhoA-GDP and its functional implications. Nat Struct Biol. 4:1997;699-703.
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0030025671
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The structure of the Escherichia col EF-Tu-EF-Ts complex at 2.5 Å resolution
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13
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0025117674
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Molecular switch for signal transduction: Structural differences between active and inactive forms of protooncogenic ras proteins
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Milburn MV, Tong L, deVos AM, Brünger A, Yamaizumi Z, Nishimura S, Kim S-H. Molecular switch for signal transduction: structural differences between active and inactive forms of protooncogenic ras proteins. Science. 247:1990;939-945.
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Milburn, M.V.1
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Kim, S.-H.7
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0025310575
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Refined crystal structure of the triphosphate conformation of H-ras p21 at 1.35 Å resolution: Implications for the mechanism of GTP hydrolysis
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Pai EF, Krengel U, Petsko GA, Goody RS, Kabsch W, Wittinghofer A. Refined crystal structure of the triphosphate conformation of H-ras p21 at 1.35 Å resolution: implications for the mechanism of GTP hydrolysis. EMBO J. 9:1990;2351-2359.
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Kabsch, W.5
Wittinghofer, A.6
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15
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Solution structure and dynamics of Ras p21-GDP determined by heteronuclear three- And four-dimensional NMR spectroscopy
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Kraulis PJ, Domaille PJ, Campbell-Burk SL, Van Aken T, Laue ED. Solution structure and dynamics of Ras p21-GDP determined by heteronuclear three- and four-dimensional NMR spectroscopy. Biochemistry. 33:1994;3515-3531.
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Kraulis, P.J.1
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Campbell-Burk, S.L.3
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Laue, E.D.5
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16
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0030589139
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iα1: A mimic of the ternary complex of Gα-catalyzed GTP hydrolysis
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of special interest. Together with [35] this is the first crystal structure of a G protein stabilized in the transient ternary complex with GTP and Pi. Substantial conformational changes in the switch II helix, which create a binding site for Pi, provides evidence that conformational changes in switch II occur before Pi release from the enzyme and may be an obligate rearrangement step that preceeds bond cleavage.
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iα1: a mimic of the ternary complex of Gα-catalyzed GTP hydrolysis. of special interest Structure. 4:1996;1277-1290 Together with [35] this is the first crystal structure of a G protein stabilized in the transient ternary complex with GTP and Pi. Substantial conformational changes in the switch II helix, which create a binding site for Pi, provides evidence that conformational changes in switch II occur before Pi release from the enzyme and may be an obligate rearrangement step that preceeds bond cleavage.
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Structure
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Berghuis, A.M.1
Lee, E.2
Raw, A.S.3
Gilman, A.G.4
Sprang, S.R.5
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0027285320
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ras with GAP, exchange factors, and its biological effector target. J Biol Chem. 268:1993;9157-9160.
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J Biol Chem
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Polakis, P.1
McCormick, F.2
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19
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0029879058
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Quantitative structure/activity analysis correlating Ras - Raf interaction in vitro to Raf activation in vivo
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of special interest. Scanning mutagenesis shows that only a subset of residues buried in the Rap1A - Raf1RBD are critical to binding.
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Block C, Janknecht R, Hermann C, Nassar N, Wittinghofer A. Quantitative structure/activity analysis correlating Ras - Raf interaction in vitro to Raf activation in vivo. of special interest Nat Struct Biol. 3:1996;244-250 Scanning mutagenesis shows that only a subset of residues buried in the Rap1A - Raf1RBD are critical to binding.
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Nat Struct Biol
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Block, C.1
Janknecht, R.2
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20
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Clackson T, Wells JA. A hot spot of binding energy in a hormone-receptor interface. Science. 267:1995;383-386.
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Science
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Clackson, T.1
Wells, J.A.2
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Differential interaction of the Ras family GTP-binding proteins H-Ras, Rap 1A, and R-Ras with the putative effector molecules Raf kinase and Ra1-guanine nucleotide exchange factor
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Herrmann C, Horn G, Spaargaren M, Wittinghofer A. Differential interaction of the Ras family GTP-binding proteins H-Ras, Rap 1A, and R-Ras with the putative effector molecules Raf kinase and Ra1-guanine nucleotide exchange factor. J Biol Chem. 271:1996;6794-6800.
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Herrmann, C.1
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Wittinghofer, A.4
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0029745645
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Ras/Rap effector specificity determined by charge reversal
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of special interest. The authors show that a residue that confers high affinity for Rap 1A upon Raf 1 Ras-binding domain resides just N-terminal to the effector loop. The crystal structure shows how this residue is involved in binding.
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Nassar N, Horn G, Herrmann C, Block C, Janknecht R, Wittinghofer A. Ras/Rap effector specificity determined by charge reversal. of special interest Nat Struct Biol. 3:1996;723-729 The authors show that a residue that confers high affinity for Rap 1A upon Raf 1 Ras-binding domain resides just N-terminal to the effector loop. The crystal structure shows how this residue is involved in binding.
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Nat Struct Biol
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Nassar, N.1
Horn, G.2
Herrmann, C.3
Block, C.4
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Wittinghofer, A.6
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23
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0031228462
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Structure of the Ras-binding of Ral guanine-nucleotid exchange factor: Implications for Ras binding and signalling
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of special interest. The solution structure of Ral-GEF Ras-binding domain is shown to be a close homolog to that of the Rap 1A Ras-binding domain, despite the weak homology between them (see [24]). Chemical shift pertubation is used to identify Ral-GEF residues that bind to Ras, although it appears that global conformation changes occur upon binding.
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Geyer M, Hermann C, Wohlgemuth SB, Wittinghofer A, Kalbitzer R. Structure of the Ras-binding of Ral guanine-nucleotid exchange factor: implications for Ras binding and signalling. of special interest Nat Struct Biol. 4:1997;694-699 The solution structure of Ral-GEF Ras-binding domain is shown to be a close homolog to that of the Rap 1A Ras-binding domain, despite the weak homology between them (see [24]). Chemical shift pertubation is used to identify Ral-GEF residues that bind to Ras, although it appears that global conformation changes occur upon binding.
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Nat Struct Biol
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Geyer, M.1
Hermann, C.2
Wohlgemuth, S.B.3
Wittinghofer, A.4
Kalbitzer, R.5
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24
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0030863611
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Three dimensional structure and of the Ras-interacting domain of RalGDS
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of special interest. This paper, in which the crystal structure of Ral-GEF Ras-binding domain is described, shows using mutagenesis and a two-hybrid screen that only a subset of the residues at the Ras-binding surface are critical to binding. A residue that confers specificity for Rap 1A in contrast to Ras is found N-terminal to the effector loop, again implicating this as a specificity region for Ras homologs.
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Huang L, Weng X, Hofer F, Margin GS, Kim S-H. Three dimensional structure and of the Ras-interacting domain of RalGDS. of special interest Nat Struct Biol. 4:1997;609-615 This paper, in which the crystal structure of Ral-GEF Ras-binding domain is described, shows using mutagenesis and a two-hybrid screen that only a subset of the residues at the Ras-binding surface are critical to binding. A residue that confers specificity for Rap 1A in contrast to Ras is found N-terminal to the effector loop, again implicating this as a specificity region for Ras homologs.
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Nat Struct Biol
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Huang, L.1
Weng, X.2
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Proteins regulating Ras and its relatives
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Boguski MS, McCormick F. Proteins regulating Ras and its relatives. Nature. 366:1993;643-654.
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Nature
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Boguski, M.S.1
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26
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0029843561
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ras and related systems
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cat) of the reaction. Markus-type parabolas are used to represent the reactant, intermediate and product state of the reaction in an energy diagram. The overall activation barrier is shown to reflect the energy of the proton transfer step, even though this step does not include the actual transition state of the hydrolysis.
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cat) of the reaction. Markus-type parabolas are used to represent the reactant, intermediate and product state of the reaction in an energy diagram. The overall activation barrier is shown to reflect the energy of the proton transfer step, even though this step does not include the actual transition state of the hydrolysis.
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Biochemistry
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Schweins, T.1
Warshel, A.2
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31
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0030036699
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Formation of a transition-state analog of the Ras GTPase reaction by Ras GDP, tetrafluoroaluminate, and GTPase-activating proteins
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Mittal R, Ahmadian MH, Goody RS, Wittinghofer A. Formation of a transition-state analog of the Ras GTPase reaction by Ras GDP, tetrafluoroaluminate, and GTPase-activating proteins. Science. 273:1996;115-117.
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Science
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Mittal, R.1
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0029861417
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The GTPase-activating protein RGS4 stabilizes the transition state for nucleotide hydrolysis
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Berman, D.M.1
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33
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0030610719
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3 mimics the transition state of protein phosphorylation in the crystal structure of nucleoside diphosphate kinase and MgADP
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0029781354
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Ras-catalyzed hydrolysis of GTP: A new perspective from model studies
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Maegley KA, Admiraal SJ, Herschlag D. Ras-catalyzed hydrolysis of GTP: a new perspective from model studies. of special interest Proc Natl Acad Sci USA. 93:1996;8160-8166 The authors summarize the arguments, experimentally based on phosphoryl transfer reactions of model compounds, for a dissociative transition state for the G-protein catalyzed GTPase reaction.
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Proc Natl Acad Sci USA
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Maegley, K.A.1
Admiraal, S.J.2
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The 2.0 Å crystal of a heterotrimeric G protein
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Lambright DG, Sondek J, Bohm A, Skiba NP, Hamm H, Sigler PB. The 2.0 Å crystal of a heterotrimeric G protein. Nature. 379:1996;311-319.
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Lambright, D.G.1
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38
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0029829561
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Crystal structure of the GTPase-activating domain of human p120GAP and implications for the interaction with Ras
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Scheffzek K, Lautwein A, Kabsch W, Ahmadian MR, Wittinghofer A. Crystal structure of the GTPase-activating domain of human p120GAP and implications for the interaction with Ras. Nature. 381:1996;591-596.
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The structure of the GTPase-activating domain from p50rhoGAP
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Crystal structure of the breakpoint cluster region-homology domain from phosphoinositide 3-kinase p85a subunit
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Koelle, M.R.1
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0030982264
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iα1: Stabilization of the transition state for GTP hydrolysis
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α GAP, RGS4. In contrast to RasGAPs, RGS4 does not appear to provide obvious catalytic assistance for the GTPase reaction but does stabilize the conformation of the three switch regions of the molecule.
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α GAP, RGS4. In contrast to RasGAPs, RGS4 does not appear to provide obvious catalytic assistance for the GTPase reaction but does stabilize the conformation of the three switch regions of the molecule.
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iα1 Arg178 - to the catalytic site of Ras, thereby confering 4-5 orders of rate accelleration.
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iα1 Arg178 - to the catalytic site of Ras, thereby confering 4-5 orders of rate accelleration.
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Scheffzek, K.1
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Structure at 1.65 Å of RhoA and its GTPase-activating protein in complex with a transition state analog
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4-. Together with the structure of CDC42Hs·p50rhoGAP complex [7], this paper provides a model of a conformational transitional that occurs within the G protein·GAP complex in progression from the ground state to the transition state.
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4-. Together with the structure of CDC42Hs·p50rhoGAP complex [7], this paper provides a model of a conformational transitional that occurs within the G protein·GAP complex in progression from the ground state to the transition state.
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Nature
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Rittinger, K.1
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48
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The 2.2 Å crystal structure of the Ras-binding domain of the serine/threonine kinase c-Raf1 in complex with Rap1A and a GTP analogue
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