Structure-stability Relationships Research Articles

Stabilization of the fibrous structure of an α-helix-forming peptide by sequence reversal

The α3-peptide, which comprises three repeats of the sequence Leu-Glu-Thr-Leu-Ala-Lys-Ala and forms an amphipathic α-helix, is unique among various α-helix-forming peptides in that it assembles into fibrous structures that can be observed by transmission electron microscopy. As part of our investigation of the structure–stability relationships of the α3-peptide, we synthesized the r3-peptide, whose amino acid sequence is the reverse of that of the α3-peptide, and we investigated the effects of sequence reversal on α-helix stability and the formation of fibrous structures. Unexpectedly, the r3-peptide formed a more-stable α-helix and longer fibers than did the α3-peptide. The stability of the r3-peptide helix decreased when the ionic strength of the buffer was increased and when the pH of the buffer was adjusted to 2 or 12. These results suggest that the r3-peptide underwent a “magnet-like” oligomerization and that an increase in the charge-distribution inequality may be the driving force for the formation of fibrous structures.

Crystal Structure of Pigment Yellow 138 Derivative

An X-ray analysis of the title pigment was undertaken to understand the structure-stability relationships. The molecule takes a non-planar structure, because of the 2-(inden-2-yl)quinoline and isoindoline fragments being twisted at the C8-N21 bond. The dihedral angles between three planar moieties are 4.2(3) and 64.4(3)°. In the crystal structure, the flat 2-(inden-2-yl)quinoline fragments are stacked opposed to each other. The isoindoline rings sandwich the solvent molecules. The solvent molecule sits on a crystallographic center of symmetry, and is disordered in the solvent channels along the c-axis.

Thermodynamic Stability of HLA-B*2705·Peptide Complexes: EFFECT OF PEPTIDE AND MAJOR HISTOCOMPATIBILITY COMPLEX PROTEIN MUTATIONS

Thermodynamic Stability of HLA-B*2705·Peptide Complexes: EFFECT OF PEPTIDE AND MAJOR HISTOCOMPATIBILITY COMPLEX PROTEIN MUTATIONS

Thermodynamic stability of HLA-B*2705. Peptide complexes. Effect of peptide and major histocompatibility complex protein mutations.

Designing synthetic vaccines from class I major histocompatibility complex (MHC)-binding antigenic peptides requires not only knowledge of the binding affinity of the designed peptide but also predicting the stability of the formed MHC-peptide complex. In order to better investigate structure-stability relationships, we have determined by circular dichroism spectroscopy the thermal stability of a class I MHC protein, HLA-B*2705, in complex with a set of 39 singly substituted peptide analogues. The influence of two anchoring side chains (P3 and P9) was studied by peptide mutation and appropriate site-directed mutagenesis of the HLA-B*2705 binding groove. The side chain at P9 is clearly the one that contributes the most to the thermal stability of the MHC-peptide complexes, as destabilization up to 25 degrees C are obtained after P9 mutation. Interestingly, structure-stability relationships do not fully mirror structure-binding relationships. As important as the C-terminal side chain are the terminal ammonium and carboxylate groups. Removal of a single H-bond between HLA-B27 and the terminal peptide moieties results in thermal destabilization up to 10 degrees C. Depending on the bound peptide and the location of the deleted H-bond, the decrease in the thermal stability of the corresponding complex is quantitatively different. The present study suggests that any peptidic amino acid at positions 3 and 9 promotes refolding of the B27-peptide complex. Once the complex is formed, the C-terminal side chain seems to play an important role for maintaining a stable complex.

Crystal structures of 3-isopropylmalate dehydrogenases with mutations at the C-terminus: crystallographic analyses of structure-stability relationships.

Thermal stability of the Thermus thermophilus isopropylmalate dehydrogenase enzyme was substantially lost upon the deletion of three residues from the C-terminus. However, the stability was partly recovered by the addition of two, four and seven amino acid residues (called HD177, HD708 and HD711, respectively) to the C-terminal region of the truncated enzyme. Three structures of these mutant enzymes were determined by an X-ray diffraction method. All protein crystals belong to space group P2(1) and their structures were solved by a standard molecular replacement method where the original dimer structure of the A172L mutant was used as a search model. Thermal stability of these mutant enzymes is discussed based on the 3D structure with special attention to the width of the active-site groove and the minor groove, distortion of beta-sheet pillar structure and size of cavity in the domain-domain interface around the C-terminus. Our previous studies revealed that the thermal stability of isopropylmalate dehydrogenase increases when the active-site cleft is closed (the closed form). In the present study it is shown that the active-site cleft can be regulated by open-close movement of the minor groove located at the opposite side to the active-site groove on the same subunit, through a paperclip-like motion.

On the Use of Path Analysis and Related Procedures for the Investigation of Ecological Problems

C) and, based on that assumption, partitioned relationships among different pathways. In this original form, path analysis was not a simultaneous method (in the Smith et al. (1997) recently drew attention to some pit- sense that all parameters were estimated simultaneously) falls that can arise when trying to predict the responses nor did it include overall tests of model fit to data. In the of experimental manipulations from nonexperimental early 1970s, more general procedures were developed for

Quantitative structure-function and structure-stability relationships of purposely modified proteins.

Quantitative structure-function relationships (QSFR) and quantitative structure-stability relationships (QSSR) analyses are described here. The objective of these analyses is to investigate and quantitatively describe the effect of the changes in structure of protein on its function or stability. During the analysis, the structural and physico-chemical properties of the amino acid residues are related to activity or stability data derived for the group of proteins containing systematic substitutions at certain positions. Four examples of the application of these analyses on the data obtained with proteins modified by site-directed mutagenesis experiments are provided. Structure-function relationships were studied for 15 mutants in position 172 of the haloalkane dehalogenase and 19 mutants in position 222 of the subtilisin, while the structure-stability relationships were investigated for 13 mutants in position 157 of phage T4 lysozyme and 18 mutants in position 49 of alpha-subunits tryptophan synthase. A total of 402 molecular descriptors derived from AAindex database were used to quantify amino acid properties and the multivariate statistical technique--partial least squares projections to latent structures--was used to identify those of them which are important for explanation of the activity and stability data. Quantitative models were developed and internally validated for every data set. The possibilities for further development of both analyses and their application for predictive and analytical purposes in protein engineering research are discussed.

Structure-stability relationships in unsaturated sulfur compounds VI. An ab initio study of the stable conformations of ( E)- and ( Z)-2-methylthio-, methylsulfinyl- and methylsulfonyl-2-butenes

The potential energy curves for the CS torsion of ( E)- and ( Z)-2-methylthio-, methylsulfinyl- and methylsulfonyl-2-butenes were calculated using ab initio methods (RHF/3-21G ∗ and 6–31G ∗). Each molecule had two energy minima symmetrically (ca. 60 °) of the s- trans (antiperiplanar) conformation. ( E)-2-methylthio-2-butene also had a third local minimum in the s- cis (synperiplanar) conformation. In 2-methylthio-2-butene the Z isomer had ca. 2 kJ mol −1 lower energy than the E isomer. In the other two compounds the E isomer was the more stable one. The energy difference between the geometric isomers in 2-methylsulfinyl- and 2-methylsulfonyl-2-butene was 6–8 and 11–14 kJ mol −1, respectively.

What are Isodesmic Reactions?

The heat of isodesmic (formal) reaction Q is systematically used as a measure of deviations from the additivity of bond energies. For molecules these Q values are applied to quantification of strain energies in cyclic compounds, to evaluation of aromaticity of benzene, to explanation of the reasons for deviation from additivity in the heats of formation for disubstituted benzenes and some alkenes. The isodesmic reactions are further used for quantification of structure-stability relationships for cations and free radicals as reactive intermediates in many organic reactions. The scales of relative thermodynamic stabilities comprising 31 cations and 33 free radicals are represented with the range of Q values ca. 225 and 90 kcal/mol respectively. The evaluated energies of aromaticity for benzene, tropylium cation, cyclopentadienyl cation are 30.5, 21.8, 20.3, and -26.8 kcal/mol, respectively.

Structure-stability relationships in some Azo disperse dyes

The synthesis of a series of dyes derived from N-substituted 1-naphthylamines as coupling components is reported. The effect of substituents in the diazo and coupling residues on the colour and the dye stability at pH 4, 7 and 9 is discussed. The main degradation product of one member of the series was identified.

New reagents for controlled release of nitric oxide. Structure-stability relationships

The synthesis and structure-stability relationships of a series of novel FK409 derivatives ( 1, 2, and 3) are described. The rates of decomposition in aqueous solution (pH 8.0, 30 °C) were parallel with those of spontaneous NO release measured by ESR spectroscopy using carboxy-PTIO. The compounds can cover a wide range of NO releasing rates by appropriate modification of the molecule.

Thermal oxidative stability of perfluoropolyalkylethers and development of quantitative structure-stability relationships

Thermal oxidative stability profiles in the presence of M-50 alloy were determined for a series of different perfluoropolyalkylether arrangements. Based on the experimental results, using molecular mechanics-molecular dynamics computations and multivariate linear regression analysis, quantitative structure-stability relationships were developed. Expression with three variables, bend, van der Waals and stretch-bend energies ( r=0.977), were shown to provide valid stability predictions. For the 10 perfluoropolyalkylethers studied, geometry-optimized molecular conformations at 313 K were determined and are presented.

Structure-stability relationships for all-silica structures.

We will discuss predictions for the stability and structures of all-silica zeolitic structures. We will show that we have derived a shell-model potential, based on ab initio calculations, which gives good predictions for the structure and stability of all-silica structures. We will compare three shell-model predictions with two rigid-ion model predictions for the structure and stability of silicates. We will show that shell-model predictions for the relative stability of zeolites are much closer to experiment than rigid-ion model predictions, due to the canceling of covalent and electrostatic terms in the shell models which does not occur in the rigid-ion models. Using the potentials with the highest predictive power on both stabilities and structures of silicates we will discuss structure-stability relationships that have been proposed in the literature.

Structure—stability relationships in unsaturated sulfur compounds Part V. An ab initio study of the stable conformations of ( E)- and ( Z)-methyl-l-propenyl sulfide, sulfoxide and sulfone

The potential energy curves for the C—S torsion of ( E)-and ( Z)-methyl-l-propenyl sulfide, sulfoxide and sulfone were calculated using ab initio methods with the 3–21G ∗ adn 6–31G ∗ basis sets. Each molecule was found to have two energy minima symmetrically (60°) on either side of the s-trans (anti-periplanar) conformation. Methyl-l-propenyl sulfide also had a third local minimum in the s-cis (syn-periplanar) conformation. In each case the E isomer was found to have a lower energy than the Z isomer. The energy difference between the geometric isomers of sulfide, sulfoxide and sulfone was 3,9–11 and 12–15 kJ mol −1, respectively.

Structure-stability relationships in unsaturated sulfur compounds: Part 2. An ab initio study of the stable conformations of divinyl sulfide, sulfoxide and sulfone

The potential energy maps for both C-S torsions of divinyl sulfide, sulfoxide and sulfone were calculated by using the gamess ab initio program and the 3-21G ∗ basis set. In each case two minima were found. In the stable conformations of divinyl sulfide the vinyl groups have turned about 45° to the opposite directions or about 40° to the same direction from the s-trans, s-trans conformation. In the most stable rotamer of divinyl sulfoxide both of the vinyl groups eclipse the SO group. In the second stable rotamer one of the vinyl groups eclipses the SO group and the other one the lone pair electrons of the sulfur atom. In the stable conformations of divinyl sulfone the vinyl groups eclipse either different SO groups or the same SO group.

Structure–stability relationships of 3-hydroxypyridin-4-one complexes

The structural features of the ligand 1-ethyl-3-hydroxy-2-methylpyridin-4-one HL1 and its tris complexes [ML13]·3H2O (M = Fe 1, Ga 2 and Al 3) have been characterized by single-crystal X-ray diffraction. The crystal structures of complexes 1–3 are isomorphous. The comparisons among HL1 and 1–3 indicate that several resonance forms play an important role in determining their structures. It is concluded that the absolute stabilities of the complexes of Al3+ and Ga3+ are similar and both greater than that of the iron(III) complex. A structural comparison between ligand HL1 and the closely related 1-butyl-3-hydroxypyridin-2-one provides an explanation for the higher affinity of 3-hydroxypyridin-4-ones for Fe3+ over 3-hydroxypyridin-2-ones. The complexes of Al3+ and Ga3+ with HL1 can be crystallized both as tri- and dodeca-hydrates. It is shown by comparing the same complex in different environments that neither the interplanar angle nor the twist angle is a reliable structural parameter to characterize a metal complex.

Structure-stability relationships of gadolinium(III) ion complexes for magnetic resonance imaging

Molecular mechanical calculations and molecular dynamics simulations, based on the AMBER force field, were used to examine the molecular structures and stabilities of nine multidentate ligands and their Gd(III) ion complexes. The magnitude of various factors determining the stability of multidentate Gd(III) complexes, including the energy loss due to change of ligand conformation by complexation, the energy gain from cation-ligand attraction, and effects of intramolecular hydrogen bonding, were calculated by molecular mechanics. The fit between the Gd cation and the binding cavity in the ligands was examined by molecular graphics techniques. Intramolecular hydrogen bonds in free ligands with amide or hydroxyl as H-bond donors usually disfavor complex formation, due to disruption of hydrogen bonds during complex formation. Intramolecular hydrogen bonds may contribute to enhance complex stability if they make the desolvation energy of the free ligands smaller. The calculated complex stabilities were in reasonable agreement with experimental log K values which were available for five of the compounds. The calculated complex stabilities of two hitherto unsynthesized covalently constrained DTPA-derivatives and a DOTA-derivative bearing phenoxy groups as pendant arms indicate that these may form Gd(III) complexes with sufficient stability for use in magnetic resonance imaging techniques.

Copper(II) complexes with N-sulphonyl amino acids. Structure-stability relationships in binary species and ternary complexes with 2,2′-bipyridine

The stability of a series of binary and ternary 2,2′-bipyridine(bipy) complexes of Cu2+ with amino acids N-substituted by an arene sulphonic group has been analysed in 0.1 mol dm–3 NaClO4 or NaNO3 at 25 °C. The stability constants determined by d.c. polarography are sensitive to the nature of the amino acid and of the aromatic moiety of the protecting group. The known lowering effect of bipy on the pK for metal-promoted sulphonamide nitrogen deprotonation in the ternary complexes is found to be quantitatively independent of the above structural features. The X-ray structure of the ternary species [Cu(bipy)(Bs-GlyNO)(H2O)][Bs-GlyNO =N-benzenesulphonylglycinate(2–)] is also presented. The crystals are monoclinic, space group P21/c, with a= 8.494(5), = 19.950(4), c= 11.295(7)A, β= 110.79(4)°, Z= 4, and R= 0.036. The structure consists of [Cu(bipy)(Bs-GlyNO)(H2O)] units in which the Cu atom exhibits a tetrahedrally distorted square-pyramidal N3O2 co-ordination.

Enzyme stabilization: state of the art

'Enzyme stabilization' is one of the most important fields in basic and applied enzymology. In basic enzymology, it is of particular relevance to understand enzyme stabilization principles first elucidating how and why the enzymes lose their biological activity and then deriving structure-stability relationships existing in enzymatic molecules. In applied enzymology, the most significant goal is to achieve useful compounds by biocatalysis. Enzymes are good catalysts in terms of high catalytic and specific activity with ability to function under mild conditions. However, they are not always ideal catalysts for practical applications because they are generally unstable and they inactivate rapidly through several mechanisms. In order to enhance enzyme stability, many strategies have been pursued in recent years. The present article is an attempt to provide detailed information about these strategies.

Structure-stability relationships of some ortho-hydrazopyrazolone derivatives with divalent metal ions

Acid dissociation constants (p K H) of a series of five compounds (I to V) of substituted 5-pyrazolone dyes have been determined potentiometrically in 75% ( v v ) dioxane/water at 30 °C and <0.1 M ionic strength. The stability constants of their 1:1 and 1:2 chelates with six divalent metal ions M 2+ have also been determined. The effect of substituents on the hydrazo-moiety of the ligand was discussed. Data were correlated and the results were used to explain the stabilization of such chelates by dative π bonding between M 2+ and the ligands.