Home About us Contact
|
Home About us Contact | ||
|
|
||
Similar Conformations (similar + conformation)
Selected AbstractsActivated Rac1, but not the tumorigenic variant Rac1b, is ubiquitinated on Lys 147 through a JNK-regulated processFEBS JOURNAL, Issue 2 2008Orane Visvikis Ubiquitination and proteasomal degradation have recently emerged as an additional level of regulation of activated forms of Rho GTPases. To characterize this novel regulatory pathway and to gain insight into its biological significance, we studied the ubiquitination of two constitutively activated forms of Rac1, i.e. the mutationally activated Rac1L61, and the tumorigenic splice variant Rac1b, which is defective for several downstream signaling pathways, including JNK activation. Whereas Rac1L61 undergoes polyubiquitination and subsequent proteasomal degradation in HEK293 cells, Rac1b is poorly ubiquitinated and appears to be much more resistant to proteasomal degradation than Rac1L61. Mutational analysis of all lysine residues in Rac1 revealed that the major target site for Rac1 ubiquitination is Lys147, a solvent-accessible residue that has a similar conformation in Rac1b. Like Rac1L61, Rac1b was found to be largely associated with plasma membrane, a known prerequisite for Rac1 ubiquitination. Interestingly, Rac1b ubiquitination could be stimulated by coexpression of Rac1L61, suggesting positive regulation of Rac1 ubiquitination by Rac1 downstream signaling. Indeed, ubiquitination of Rac1L61 is critically dependent on JNK activation. In conclusion: (a) Rac1b appears to be more stable than Rac1L61 with regard to the ubiquitin,proteasome system, and this may be of importance for the expression and tumorigenic capacity of Rac1b; and (b) ubiquitination of activated Rac1 occurs through a JNK-activated process, which may explain the defective ubiquitination of Rac1b. The JNK-dependent activation of Rac1 ubiquitination would create a regulatory loop allowing the cell to counteract excessive activation of Rac1 GTPase. [source] Crystal structure of human Rad GTPase of the RGK-familyGENES TO CELLS, Issue 8 2006Arry Yanuar Rad (Ras associated with diabetes) is an RGK-family small GTPase that is over-expressed in the skeletal muscle of humans with type II diabetes. Unlike other small GTPases, RGK family members including Rad lack several conserved residues in the GTPase domain. Here, we report the crystal structure of the GTPase domain of human Rad in the GDP-bound form at 1.8 Å resolution. The structure revealed unexpected disordered structures of both switches I and II. We showed that the conformational flexibility of both switches is caused by non-conservative substitutions in the G2 and G3 motifs forming the switch cores together with other substitutions in the structural elements interacting with the switches. Glycine-rich sequences of the switches would also contribute to the flexibility. Switch I lacks the conserved phenylalanine that makes non-polar interactions with the guanine base in H-Ras. Instead, water-mediated hydrogen bonding interactions were observed in Rad. The GDP molecule is located at the same position as in H-Ras and adopts a similar conformation as that bound in H-Ras. This similarity seems to be endowed by the conserved hydrogen bonding interactions with the guanine base-recognition loops and the magnesium ion that has a typical octahedral coordination shell identical to that in H-Ras. [source] Structure of cyclized green fluorescent proteinACTA CRYSTALLOGRAPHICA SECTION D, Issue 9 2002Andreas Hofmann Crystals of cyclic green fluorescent protein (cGFP) engineered by the previously reported split intein technology [Iwai et al. (2001), J. Biol. Chem.276, 16548,16554] were obtained and the structure was solved using molecular replacement. Although the core of the protein can unambiguously be fitted from the first to the last residue of the genuine sequence, the electron density in the region of the linker peptide is rather poor owing to the high water content of the crystals. Therefore, it is concluded that this part of the protein is highly disordered in the present structure and is very flexible. This is supported by the absence of crystal contacts in the linker-peptide region and the fact that the core of the protein exhibits a very similar conformation to that known from other GFP structures, thereby not implicating any constraints arising from the presence of the artificial linker. Nevertheless, the density is consistent with the loop being intact, as confirmed by mass spectroscopy of dissolved crystals. The present structure contains an antiparallel cGFP dimer where the dimer interface is clearly different from other crystal structures featuring two GFP molecules. This adds further support to the fact that the cylinder surface of GFP is rather versatile and can employ various polar and non-polar patches in protein,protein interactions. [source] Importance of Interaction between C1 Domain and Lipids in Protein Kinase C, Activation: Hydrophobic Side Chain Direction in Isobenzofuranone Ligands Controls Enzyme Activation LevelCHEMMEDCHEM, Issue 7 2007Go Hirai Dr. Substituent direction is important: Type A,D isobenzofuranone derivatives were synthesized with differently directed hydrophobic alkyl side chains. These ligands bind in a similar conformation to protein kinase C, but have contrasting activation abilities, possibly owing to different interaction of the side chain with the membrane lipid. [source] A list of organic kryptoracematesACTA CRYSTALLOGRAPHICA SECTION B, Issue 1 2010László Fábián A list of 181 organic kryptoracemates has been compiled. This class of crystallographic oddities is made up of racemic compounds (i.e. pairs of resolvable enantiomers) that happen to crystallize in Sohnke space groups (i.e. groups that include only proper symmetry operations). Most (151) of the 181 structures could have crystallized as ordered structures in non-Sohnke groups. The remaining 30 structures do not fully meet this criterion but would have been classified as kryptoracemates by previous authors. Examples were found and checked with the aid of available software for searching the Cambridge Structural Database, for generating and comparing InChI strings, and for validating crystal structures. The pairs of enantiomers in the true kryptoracemates usually have very similar conformations; often the match is near-perfect. There is a pseudosymmetric relationship of the enantiomers in about 60% of the kryptoracemate structures, but the deviations from inversion or glide symmetry are usually quite easy to spot. Kryptoracemates were found to account for 0.1% of all organic structures containing either a racemic compound, a meso molecule, or some other achiral molecule. The centroid of a pair of enantiomers is more likely (99.9% versus 99% probability) to be located on an inversion center than is the centroid of a potentially centrosymmetric molecule. [source] Powder X-ray studies of meso -hexamethyl propylene amine oxime (meso -HMPAO) in two different phasesACTA CRYSTALLOGRAPHICA SECTION C, Issue 9 2010Mahmoud Al-Ktaifani Two different forms of meso -3,3,-[2,2-dimethylpropane-1,3-diylbis(azanediyl)]dibutan-2-one dioxime, commonly called meso -hexamethyl propylene amine oxime (HMPAO), C13H28N4O2, designated , and ,, were isolated by fractional crystallization and their crystal structures were determined by powder X-ray diffraction using the direct-space method with the parallel tempering algorithm. The , form was first crystallized from acetonitrile solution, while the , form was obtained by recrystallization of the , phase from diethyl ether. The , form crystallizes in the triclinic system (space group P), with one molecule in the asymmetric unit, while the crystal of the , form is monoclinic (space group P21/n), with one molecule in the asymmetric unit. In both phases, the molecules have similar conformations and RS/EE geometric isomerism. The crystal packing of the two phases is dominated by intermolecular hydrogen-bonding interactions between the two O,H oxime groups of an individual molecule and the amine N atoms of two different adjacent molecules, which lead to segregation of extended poly(meso -HMPAO) one-dimensional chains along the c direction. The structures of the two phases are primarily different due to the different orientations of the molecules in the chains. [source] Ring conformations and intermolecular interactions in two fused dibenzoazocinesACTA CRYSTALLOGRAPHICA SECTION C, Issue 6 2010Andrés F. Yepes 5-Acetyl-2-chloro-8,11-dimethyl-5,6,11,12-tetrahydrodibenzo[b,f]azocine, C19H20ClNO, (I), crystallizes as a single fully ordered isomer, but 14-acetyl-8,11-dimethyl-7,8,13,14-tetrahydrobenzo[f]naphtho[1,2- b]azocine,14-acetyl-8,9-dimethyl-7,8,13,14-tetrahydrobenzo[f]naphtho[1,2- b]azocine (74/26), C23H23NO, (II), exhibits threefold whole-molecule disorder involving both configurational and structural isomers. In (I) and in the predominant form of (II), the azocine rings adopt very similar conformations, forming boat-shaped rings having approximate twofold rotational symmetry. There are no direction-specific intermolecular interactions in the crystal structure of (I), but the molecules of (II) are weakly linked into chains by an aromatic ,,, stacking interaction. The compounds were made under green conditions using an acid-catalysed cyclization process having very high atom utilization. [source] Structure,activity relationships in 4- and 5-androstene: 3,-acetoxy-17-methyl-17-oxo-16,17-seco-5-androstene-16-carbonitrile and 17-methyl-3,17-dioxo-16,17-seco-4-androstene-16-carbonitrileACTA CRYSTALLOGRAPHICA SECTION C, Issue 9 2004an Lazar The title compounds, C22H31NO3 and C20H27NO2, have similar conformations except in the molecular geometry and the bonding of two of the rings. These differences lead to marked differences in the biological activities of these compounds. Molecules of both compounds are linked by weak C,H,O hydrogen bonds in the crystal structures. [source] Dibothrioclinin I and II, epimers from Gerbera piloselloides (L.) CassACTA CRYSTALLOGRAPHICA SECTION C, Issue 10 2003Cheng Wang Dibothrioclinin I and II, namely (+)-(11R,12S,25R,27S)- and (±)-(11RS,12RS,25RS,27SR)-3,3,7,17,21-pentamethyl-4,12,18,26-tetraoxaheptacyclo[15.11.1.02,15.05,14.06,11.019,28.020,25]nonacosa-5(14),6,8,10,19(28),20,22,24-octaene-13,27-dione, respectively, are C30H28O6 epimers which are derived from two bothrioclinin moieties joined so as to create an additional six-membered ring. Structurally, the epimers differ only by inversion at one C atom of a central ring junction and the corresponding six-membered rings have similar conformations in each molecule, except for one ring adjacent to this inversion site. [source] Vibrational 13C-cross-polarization/magic angle spinning NMR spectroscopic and thermal characterization of poly(alanine-glycine) as model for silk I Bombyx mori fibroinBIOPOLYMERS, Issue 5 2003Patrizia Monti Abstract This study focuses on the conformational characterization of poly(alanine-glycine) II (pAG II) as a model for a Bombyx mori fibroin silk I structure. Raman, IR, and 13C-cross-polarization/magic angle spinning NMR spectra of pAG II are discussed in comparison with those of the crystalline fraction of B. mori silk fibroin (chymotryptic precipitate, Cp) with a silk I (silk I-Cp) structure. The spectral data give evidence that silk I-Cp and the synthetic copolypeptide pAG II have similar conformations. Moreover, the spectral findings reveal that silk I-Cp is more crystalline than pAG II; consequently, the latter contains a larger amount of the random coil conformation. Differential scanning calorimetry measurements confirm this result. N-Deuteration experiments on pAG II allow us to attribute the Raman component at 1320 cm,1 to the amide III mode of a ,-turn type II conformation, thus confirming the results of those who propose a repeated ,-turn type II structure for silk I. The analysis of the Raman spectra in the ,NH region confirms that the silk I structure is characterized by the presence of different types of H-bonding arrangements, in agreement with the above model. © 2003 Wiley Periodicals, Inc. Biopolymers (Biospectroscopy) 72: 329,338, 2003 [source] Sterically Crowded peri -Substituted Naphthalene Phosphines and their PV DerivativesCHEMISTRY - A EUROPEAN JOURNAL, Issue 25 2010Fergus Abstract Three sterically crowded peri -substituted naphthalene phosphines, Nap[PPh2][ER] (Nap=naphthalene-1,8-diyl; ER=SEt, SPh, SePh) 1,3, which contain phosphorus and chalcogen functional groups at the peri positions have been prepared. Each phosphine reacts to form a complete series of PV chalcogenides Nap[P(E,)(Ph2)(ER)] (E,=O, S, Se). The novel compounds were fully characterised by using X-ray crystallography and multinuclear NMR spectroscopy, IR spectroscopy and MS. X-ray data for 1, 2, n,O, n,S, n,Se (n=1,3) are compared. Eleven molecular structures have been analysed by naphthalene ring torsions, peri -atom displacement, splay angle magnitude, X,,,E interactions, aromatic ring orientations and quasi-linear arrangements. An increase in the congestion of the peri region following the introduction of heavy chalcogen atoms is accompanied by a general increase in naphthalene distortion. P,,,E distances increase for molecules that contain bulkier atoms at the peri positions and also when larger chalcogen atoms are bound to phosphorus. The chalcogenides adopt similar conformations that contain a quasi-linear E,,,PC fragment, except for 3,O, which displays a twist-axial-twist conformation resulting in the formation of a linear O,,,SeC alignment. Ab initio MO calculations performed on 2,O, 3,O, 3,S and 3,Se reveal Wiberg bond index values of 0.02 to 0.04, which indicates only minor non-bonded interactions; however, calculations on radical cations of 3,O, 3,S and 3,Se reveal increased values (0.14,0.19). [source] | ||||||||||||||||||||||