Modular design of synthetic protein mimics. Crystal structures, assembly, and hydration of two 15- and 16-residue apolar, leucyl-rich helical peptides

Two IS- and 16-residue peptides containing a-aminoisobutyric acid (Aib) have been synthesized, as part of a strategy to construct stereochemically rigid peptide helices, in a modular approach to design of protein mimics. The peptides Boc-(Val-Ala-Leu-Aib),-OMe ( I ) and Boc-Val-Ala-Leu-Aib-Val-Ala-Leu-(Val-Ala-Leu-Aib()11z)- OhaMvee been crystallized.Both crystals are stable only in the presence of mother liquor or water. The crystal data are as follows. I: C78H140N16019~2H20,P2,, a = 16.391 (3) A, b = 16.860 (3) A, c = 18.428 (3) A, p = 103.02 (I)O, Z = 2, R = 9.6% for 3445 data with lFol >30(F), resolution 0.93 A. 11: C7,Hl,,N,S018.7.5H,0, C2221, a = 18.348 ( 5 ) A, b = 47.382 (1 1) A, c = 24.157 ( 5 ) A, Z =8, R = l0,6%, for 3147 data with lFol > 3a(F), resolution 1.00 A. The 15-residue peptide (11) is entirely a helical, while the 16-residue peptide ( I ) has a short segment of 310 helix at the N terminus. The packing of the helices in the crystals is rather incfficicnt with no particular attractions between Leu-Leu side chains, or any other pair. Both crystals have fairly large voids, which are filled with water molecules in a disordered fashion. Water molecule sites near the polar head-to-tail regions are well detcrmined, those closer to the hydrophobic side chains less so and a number of possible water sites in the remaining "empty" space are not determined. No interdigitation of Leu side chains is observed in the crystal as is hypothesized in the "leucine zipper" class of DNA binding proteins.

Peptide mimics for structural features in proteins. Crystal structures of three heptapeptide helices with a C-terminal 6-->1 hydrogen bond.

The crystal structure determination of three heptapeptides containing alpha-aminoisobutyryl (Aib) residues as a means of helix stabilization provides a high-resolution characterization of 6-->1 hydrogen-bonded conformations, reminiscent of helix-terminating structural features in proteins. The crystal parameters for the three peptides, Boc-Val-Aib-X-Aib-Ala-Aib-Y-OMe, where X and Y are Phe, Leu (I), Leu, Phe (II) and Leu, Leu (III) are: (I) space group P1, Z = 1, a = 9.903 A, b = 10.709 A, c = 11.969 A, alpha = 102.94 degrees, beta = 103.41 degrees, gamma = 92.72 degrees, R = 4.55%; (II) space group P21, Z = 2, a = 10.052 A, b = 17.653 A, c = 13.510 A, beta = 108.45 degrees, R = 4.49%; (III) space group P1, Z = 2 (two independent molecules IIIa and IIIb in the asymmetric unit), a = 10.833 A, b = 13.850 A, c = 16.928 A, alpha = 99.77 degrees, beta = 105.90 degrees, gamma = 90.64 degrees, R = 8.54%. In all cases the helices form 3(10)/alpha-helical (or 3(10)helical) structures, with helical columns formed by head-to-tail hydrogen bonding. The helices assemble in an all-parallel motif in crystals I and III and in an antiparallel motif in II. In the four crystallographically characterized molecules, I, II, IIIa and IIIb, Aib(6) adopts a left-handed helical (hL) conformation with positive phi, psi values, resulting in 6-->1 hydrogen-bond formation between Aib(2) CO and Leu(7)/Phe(7) NH groups. In addition a 4-->1 hydrogen bond is seen between Aib(3) CO and Aib(6) NH groups. This pattern of hydrogen bonding is often observed at the C-terminus of helices proteins, with the terminal pi-type turn being formed by four residues adopting the hRhRhRhL conformation.

Anomalous temperature dependence of Fermi-edge singularity in modulation-doped AlGaAs/InGaAs/GaAs hetero-structures

The temperature and power dependence of Fermi-edge singularity (FES) in high-density two-dimensional electron gas, specific to pseudomorphic AlxGa1-xAs/InGa1-yAs/GaAs heterostructures is studied by photoluminescence (PL). In all these structures, there are two prominent transitions E-11 and E-21 considered to be the result of electron-hole recombination from first and second electron sub-bands with that of first heavy-hole sub-band. FES is observed approximately 5-10 meV below the E-21 transition. At 4.2 K, FES appears as a lower energy shoulder to the E-21 transition. The PL intensity of all the three transitions E-11, FES and E-21 grows linearly with excitation power. However, we observe anomalous behavior of FES with temperature. While PL intensity of E-11 and E-21 decrease with increasing temperature, FES transition becomes stronger initially and then quenches-off slowly (till 40K). Though it appears as a distinct peak at about 20 K, its maximum is around 7 - 13 K.

Crystal structures of a nonapeptide helix containing alpha,alpha-di-n-butylglycine (Dbg), Boc-Gly-Dbg-Ala-Val-Ala-Leu-Aib-Val-Leu-OMe

Two crystals structures of a nonapeptide (anhydrous and hydrated) containing the amino acid residue alpha, alpha-di-n-butylglycyl, reveal a mixed 3(10)/alpha-helical conformation. Residues 1-7 adopt phi, psi values in the helical region, with Val(8) being appreciably distorted. The Dbg residue has phi, psi values of -40, -37 degrees and -46, -40 degrees in two crystals with the two butyl side chains mostly extended in each. Peptide molecules in the crystals pack into helical columns. The crystal parameters are C50H91N9O12, space group P2(1), with a = 9.789(1) Angstrom, b = 20.240(2) Angstrom, c = 15.998(3) Angstrom, beta = 103.27(1); Z = 2, R = 10.3% for 1945 data observed >3 sigma(F) and C50H91N9O12. 3H(2)O, space group P2(1), with a = 9.747(3) Angstrom, b = 21.002(8) Angstrom, c = 15.885(6) Angstrom, beta = 102.22(3)degrees, Z = 2, R = 13.6% for 2535 data observed >3 sigma(F). The observation of a helical conformation at Dbg suggests that the higher homologs in the alpha, alpha-dialkylated glycine series also have a tendency to stabilize peptide helices. (C) Munksgaard 1996.

Chain structures in alkali metal borophosphates: synthesis and characterization of K3[BP3O9(OH)3] and Rb3[B2P3O11(OH)2]

Two new alkali metal borophosphates, K-3[BP(3)o(9)(OH)(3)] and Rb-3[B2P3O11(OH)(2)], were synthesized by applying solvothermal techniques using ethanol as solvent. The crystal structures were solved by means of single-crystal X-ray diffraction (K-3[BP3O9(OH)(3)], monoclinic, C2/c (No. 15), a = 2454.6(8) pm, b = 736.3(2) pm, c = 1406.2(4) pm, beta = 118.35(2)degrees, Z = 8; Rb-3[B2P3O11(OH)(2)], monoclinic, P2(1)/c (No. 14), a = 781.6(2) pm, b:= 667.3(2) pm, c = 2424.8(5) pm, beta = 92.88(1)degrees, Z = 4). Both crystal structures comprise borophosphate chain anions. While for the rubidium compound a loop-branched chain motif is found as common for most of the chain anions in alkali metal borophosphates, the crystal structure of the potassium phase comprises the first open-branched chain with the highest phosphate content found so far in this group of compounds. Both chain anions are Closely related to known anhydrous or hydrated phases, and the structural relations are discussed in terms of how the presence of OH groups and hydrogen bonds as well as number, charge, and size of charge balancing cations influence the 3D structural arrangement. The anionic entities are classified in terms of general principles of structural systematics for borophosphates.

Disallowed Ramachandran Conformations of Amino Acid Residues in Protein Structures

An analysis of the nature and distribution of disallowed Ramachandran conformations of amino acid residues observed in high resolution protein crystal structures has been carried out. A data set consisting of 110 high resolution, non-homologous, protein crystal structures from the Brookhaven Protein Data Bank was examined. The data set consisted of a total of 18,708 non-Gly residues, which were characterized on the basis of their backbone dihedral angles (φ, ψ). Residues falling outside the defined “broad allowed limits” on the Ramachandran map were chosen and the reportedB-factor value of the α-carbon atom was used to further select well defined disallowed conformations. The conformations of the selected 66 disallowed residues clustered in distinct regions of the Ramachandran map indicating that specific φ, ψ angle distortions are preferred under compulsions imposed by local constraints. The distribution of various amino acid residues in the disallowed residue data set showed a predominance of small polar/charged residues, with bulky hydrophobic residues being infrequent. As a further check, for all the 66 cases non-hydrogen van der Waals short contacts in the protein structures were evaluated and compared with the ideal “Ala-dipeptide” constructed using disallowed dihedral angle (φ, ψ) values. The analysis reveals that short contacts are eliminated in most cases by local distortions of bond angles. An analysis of the conformation of the identified disallowed residues in related protein structures reveals instances of conservation of unusual stereochemistry.

Conformation of di-n-propylglycine residues (Dpg) in peptides: crystal structures of a type I 'beta-turn forming tetrapeptide and an alpha-helical tetradecapeptide

The crystal structures of two oligopeptides containing di-n-propylglycine (Dpg) residues, Boc-Gly-Dpg-Gly-Leu-OMe (1) and Boc-Val-Ala-Leu-Dpg-Val-Ala-Leu-Val-Ala-Leu-Dpg-Val-Ala-Leu-OMe (2) are presented. Peptide 1 adopts a type I' beta-turn conformation with Dpg(2)-Gly(3) at the corner positions. The 14-residue peptide 2 crystallizes with two molecules in the asymmetric unit, both of which adopt alpha-helical conformations stabilized by 11 successive 5 -> 1 hydrogen bonds. In addition, a single 4 -> 1 hydrogen bond is also observed at the N-terminus. All live Dpg residues adopt backbone torsion angles (phi, psi) in the helical region of conformational space. Evaluation of the available structural data on Dpg peptides confirm the correlation between backbone bond angle N-C-alpha-C' (tau) and the observed backbone phi,psi values. For tau > 106 degrees, helices are observed, while fully extended structures are characterized by tau < 106 degrees. The mean r values for extended and folded conformations for the Dpg residue are 103.6 degrees +/- 1.7 degrees and 109.9 degrees +/- 2.6 degrees, respectively. Copyright (C) 2007 European Peptide Society and John Wiley & Sons, Ltd.

Synthesis, Structure, Spirocyclization Mechanism, and Glutathione Peroxidase-like Antioxidant Activity of Stable Spirodiazaselenurane and Spirodiazatellurane

The first examples of stable spirodiazaselenurane and spirodiazatellurane were synthesized by oxidative spirocyclization of the corresponding diaryl selenide and telluride and were structurally characterized. X-ray crystal structures of the spirodiazaselenurane and spirodiazatellurane suggest that the structures are distorted trigonal bipyramidal (TBP) with the electronegative nitrogen atoms occupying the apical positions and two carbon atoms and the lone pair of Se/Te occupying the equatorial positions. Interestingly, the spirodiazatellurane underwent spontaneous chiral resolution during crystallization, and the absolute configurations of its enantiomers were confirmed by single-crystal X-ray analyses. A detailed mechanistic study indicates that the cyclization to spirodiazaselenurane and spirodiazatellurane occurs via selenoxide and telluroxide intermediates. The chalcogenoxides cyclize to the corresponding spiro compounds in a stepwise manner via the involvement of hydroxyl chalcogenurane intermediates, and the activation energy for them spirocyclization reaction decreases in the order S > Se > Te. In addition to the synthesis, characterization, and mechanism of cyclization, the glutathione peroxidase (GPx) mimetic activity of the newly synthesized compounds was evaluated. These studies suggest that the tellurium compounds are more effective as GPx mimics than their selenium counterparts due to the fast oxidation of the tellurium center in the presence of peroxide and the involvement of an efficient redox cycle between the telluride and telluroxide intermediate.

Itämafia : Uhkakuvapolitiikka, rikosilmiöt ja kulttuuriset merkitykset

The Eastern Mafia Threat policy, crime phenomena, and cultural meanings An interdisciplinary research on the crime phenomena and the threat policy relating to the organized crime and the mafia of Russia and Estonia is based on 151 expert interviews, statistics, documents, research literature, and press material. The main part of the material consists of interviews of the Finnish, Estonian and Russian police authorities specialized in the problem of organized crime, and the reports on the crime situation drawn up in the Finnish diplomatic representations in Tallinn and St Petersburg. The interviews have been gathered in the years 1996-2001. The main theoretical tools of the research are constructivist research on social problems, and political psychology. Definitional processes of social problems and cultural semantic structures behind them are identified in the analysis and connected to the analysis of the crime cases. Both in the Anglo-American and Russian cultural frames there appears an inflated and exaggerated talk, according to which the mafia rules everything in Russia and is spreading everywhere. There is the traditional anti-Semitic paranoia in the core of this cultural symbiosis produced by Russian legal nihilism, the theory of totalitarianism of Sovietology, and the inertia of Russian anti-capitalism. To equate the Sicilian Mafia with Russia is an anachronism, since no empirical proof of systematic uncontrolled violence or absolute power vacuum in Russia can be found. In the Anglo-American policy of threat images, "the Russian mafia" was seen as a commodified conspiracy theory, which the police, the media, and the research took advantage of, blurring the line between fact and fiction. In Finland, the evolution of the policy of threat images proceeded in three phases: Initially, extensive rolling of refugees and criminals from Russia to Finland was emphasized in the beginning of the 1990's. In the second phase, the eastern mafia was said to infiltrate all over Finnish society and administration. Finland was, however, found immune to this kind of spreading. In the third phase, in the 21st century, the organized crime of Finland was said to be lead from abroad. In Finland, the policy of threat images was especially canalised to moral panics connected to "eastern prostitution". In Estonia, the policy of threat images emphasized the crime organized by the Russian authorities and politicians in order to weaken Estonia. In Russia, the policy of threat images emphasized the total criminalizing of society caused by criminal capitalism. In every country, the policy of threat images was affected by a so-called large-group identity, a term by Vamik Volkan, in which a so-called chosen trauma caused a political paranoia of an outer and inner danger. In Finland, procuring, car theft, and narcotics crimes were at their widest arranged by the Finnish often with the help of the Estonians. The Russians had no influence in the most serious violent crimes in Finland, although the number of assassinations were at least 5, 000 in Russia in the 1990's. In Russia, the assassinations were on one hand connected to marital problems, on the other hand to the pursuit of public attention and a hoped-for effect by the aid of the murder of an influential person. In the white-collar crime phenomena between Finland and Russia, the Finnish state and Finnish corporations gained remarkable benefit of the frauds aimed at the states of the Soviet Union and Russia in 1980's-21st century. The situation of Estonia was very difficult compared to that of Russia in the 1990's, which was manifested in the stagnation of the Estonian police and judicial authorities, the crimes of the police and the voluntary paramilitary organization, bomb explosions, the rebellion called "the jaeger crisis" in the voluntary paramilitary organization, and the "blood autumn" of Eastern Virumaa, in other words terror. The situation of Estonia had a powerful effect on the crime situation of Finland and on the security of the Finnish diplomats. In the continuum of the Finnish policy of threat images, Russia and the Russians were, however, presented as a source of a marked danger.

The syntheses, characterizations, X-ray crystal structures and properties of Cu(I) complexes of a bis-bidentate schiff base ligand

Bis-bidentate Schiff base ligand L and its two mononuclear complexes [CuL(CH3CN)(2)]ClO4 (1)and [CuL(PPh3)(2)]ClO4 (2)have been prepared and thoroughly characterized by elemental analyses, IR, UV-Vis, NMR spectroscopy and X-ray diffraction analysis. In both the complexes the metal ion auxiliaries adopt tetrahedral coordination environment. Their reactivity, electrochemical and photophysical behavior have been studied. Complex 1 shows reversible Cu-II/I couple with potential 0.74 V versus Ag/AgCl in CH2Cl2. At room temperature L is weakly fluorescent in CH2Cl2, however in Cu(I)complexes 1 and 2 the emission in quenched. (C) 2009 Elsevier B. V. All rights reserved.

Structural plasticity and enzyme action: Crystal structures of Mycobacterium tuberculosis peptidyl-tRNA hydrolase

Peptidyl-tRNA hydrolase cleaves the ester bond between tRNA and the attached peptide in peptidyl-tRNA in order to avoid the toxicity resulting from its accumulation and to free the tRNA available for further rounds in protein synthesis. The structure of the enzyme from Mycobacteritan tuberculosis has been determined in three crystal forms. This structure and the structure of the enzyme frorn Escherichia coli in its crystal differ substantially on account of the binding of the C terminus of the E. coli enzyme to the peptide-binding site of a neighboring molecule in the crystal. A detailed examination of this difference led to an elucidation of the plasticity of the binding site of the enzyme. The peptide-binding site of the enzyme is a cleft between the body, of the molecule and a polypepticle Y stretch involving a loop and a helix. This stretch is in the open conformation when the enzyme is in the free state as in the crystals of M. tuberculosis peptidyl-tRNA hydrolase. Furthermore, there is no physical continuity between the tRNA and the peptide-binding sites. The molecule in the E. coli crystal mimics the peptide-bound enzyme molecule. The peptide stretch referred to earlier now closes on the bound peptide. Concurrently, a channel connecting the tRNA and the peptide-binding site opens primarily through the concerted movement of two residues. Thus, the crystal structure of M. tuberculosis peptidyl-tRNA hydrolase when compared with the crystal structure of the E. coli enzyme, leads to a model of structural changes associated with enzyme action on the basis of the plasticity of the molecule. (c) 2007 Elsevier Ltd. All rights reserved.

Solution structures of conformationally equilibrium forms of holo-acyl carrier protein (PfACP) from Plasmodium falciparum provides insight into the mechanism of activation of ACPs

Acyl Carrier Protein (ACP) from the malaria parasite, Plasmodium falciparum (PfACP) in its holo form is found to exist in two conformational states in solution. Unique 3D solution structures of holo-PfACP have been determined for both equilibrium conformations, using high-resolution NMR methods. Twenty high-resolution solution structures for each of the two forms of holo-PfACP have been determined on the basis of 1226 and 1218 unambiguously assigned NOEs (including NOEs between 4 '-phosphopantetheine prosthetic group (4 '-PP) and protein), 55 backbone dihedral angles and 26 hydrogen bonds. The atomic rmsd values of the determined structures of two equilibrium forms, about the mean coordinates of the backbone and heavy atoms, are 0.48 +/- 0.09 and 0.92 +/- 0.10 and 0.49 +/- 0.08 and 0.97 +/- 0.11 angstrom, respectively. The interaction of 4 '-PP with the polypeptide backbone is reported here for the first time for any of the ACPs. The structures of holo-PfACP consist of three well-defined helices that are tightly packed. The structured regions of the molecule are stabilized by extensive hydrophobic interactions. The difference between the two forms arises from a reorientation of the 4 '-PP group. The enthalpy difference between the two forms, although small, implies that a conformational switch is essential for the activation of holo-ACP. Sequence and structures of holo-PfACP have been compared with those of the ACPs from type I and type II fatty acid biosynthesis pathways (FAS), in particular with the ACP from rat and the butyryl-ACP from E. coli. The PfACP structure, thus determined has several novel features hitherto not seen in other ACPs.

Study of (Ba3MMWO9)-M-II-W-IV (M-II = Ca, Zn; M-IV = Ti, Zr) perovskite oxides: Competition between 3C and 6H perovskite structures

We describe an investigation of (Ba3MMWO9)-M-II-W-IV oxides for M-II = Ca, Zn, and other divalent metals and M-IV = Ti, Zr. In general, a 1:2-ordered 6H (hexagonal, P6(3)/mmc) perovskite structure is stabilized at high temperatures (1300 degrees C) for all of the (Ba3MTiWO9)-Ti-II oxides investigated. An intermediate phase possessing a partially ordered 1:1 double perovskite (3C) structure with the cation distribution, Ba-2(Zn2/3Ti1/3)(W2/3Ti1/3)O-6, is obtained at 1200 degrees C for Ba3ZnTiWO9. Sr substitution for Ba in the latter stabilizes the cubic 3C structure instead of the 6H structure. A metastable Ba3CaZrWO9 that adopts the 3C (cubic, Fm (3) over barm) structure has also been synthesized by a low-temperature metathesis route. Besides yielding several new perovskite oxides that may be useful as dielectric ceramics, the present investigation provides new insights into the complex interplay of crystal chemistry (tolerance factor) and chemical bonding (anion polarization and d(0)-induced distortion of metal-oxygen octahedra) in the stabilization of 6H versus 3C perovskite structures for the (Ba3MMWO9)-M-II-W-IV series.

Identification of carbohydrate structures as receptors for localised adherent enteropathogenic Escherichia coli

Enteropathogenic Escherichia coli strains of diffused adherent (DA) and localised adherent (LA) phenotypes were tested for their ability to bind to glycolipids. DA strains did not bind to the glycolipids tested, while LA strains bound to asialo GM1, asialo GM2, globoside and lacto-N-neotetraose in decreasing order of avidity. The minimum common sequence among the four glycolipids could be delineated as GalNac β 1–4 Gal as the binding epitope with GalNac β 1–3 Gal and GlcNac β 1–3 Gal serving as relatively weaker binders. The binding was not inhibited by a variety of free oligosaccharides or by the neoglycoproteins tested. Adhesion-negative mutants of an enteropathogenic LA strain showed a markedly reduced binding to asialo GM1 indicating that the recognition of GalNac β 1–4 Gal was correlated with the ability to adhere to HeLa cells. Thus recognition and binding to glycolipids could play an important role in colonisation through adherence to intestinal surfaces.

Note on the locally product and almost locally product structures

This paper is concerned with a study of some of the properties of locally product and almost locally product structures on a differentiable manifold X n of class C k . Every locally product space has certain almost locally product structures which transform the local tangent space to X n at an arbitrary point P in a set fashion: this is studied in Theorem (2.2). Theorem (2.3) considers the nature of transformations that exist between two co-ordinate systems at a point whenever an almost locally product structure has the same local representation in each of these co-ordinate systems. A necessary and sufficient condition for X n to be a locally product manifold is obtained in terms of the pseudo-group of co-ordinate transformations on X n and the subpseudo-groups [cf., Theoren (2.1)]. Section 3 is entirely devoted to the study of integrable almost locally product structures.