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PubMed2002

The structure of orange HgI2. II. Diamond-type structure and twinning.

The metastable orange crystals of HgI(2) comprise three different crystal structures all of which are built from corner-linked Hg(4)I(10) supertetrahedra. Two of the structures are end members with the maximum degree of order (MDO) of a polytypic layer structure. In this paper, the third structure (D) determined from X-ray diffraction, a crystal chemical discussion of the four known tetrahedral HgI(2) structures, and a twinning model are presented. All the various diffraction results published during the past 70 years are now explained. The Hg(4)I(10) supertetrahedra of the tetragonal structure D are corner-linked into two interpenetrating diamond-type networks. The stable red form and the three orange structures show the same cubic densest packing of I atoms and differ only in the distribution of Hg atoms in the tetrahedral voids. Transformations between the structures may involve only movements of Hg atoms, as implied by larger thermal displacement parameters of Hg than of I. A multiply twinned conglomerate of MDO1, MDO2 and D, each structure occurring in three orientations, results in metrically cubic crystals whose Bragg reflections are very close to reciprocal lattice points.

Journal Article↗
PubMed1999

Structure and function of the N-linked glycans of HBP/CAP37/azurocidin: crystal structure determination and biological characterization of nonglycosylated HBP.

The three N-glycosylation sites of human heparin binding protein (HBP) have been mutated to produce a nonglycosylated HBP (ng-HBP) mutant. ng-HBP has been crystallized and tested for biological activity. Complete X-ray data have been collected to 2.1 A resolution, and the structure has been fully refined to an R-factor of 18.4% (R(free) 27.7%). The ng-HBP structure reveals that neither the secondary nor tertiary structure have changed due to the removal of the glycosylation, as compared to the previously determined glycosylated HBP structure. Although the primary events in N-linked glycosylation occurs concomitant with polypeptide synthesis and therefore possesses the ability to influence early events in protein folding, we see no evidence of glycosylation influencing the structure of the protein. The root-mean-square deviation between the superimposed structures was 0.24 A (on C alpha atoms), and only minor local structural differences are observed. Also, the overall stability of the protein seems to be unaffected by glycosylation, as judged by the B-factors derived from the two X-ray structures. The flexibility of a glycan site may be determined by the local polypeptide sequence and structure rather than the glycan itself. The biological in vitro activity assay data show that ng-HBP, contrary to glycosylated HBP, mediates only a very limited stimulation of the lipopolysaccharide induced cytokine release from human monocytes. In animal models of fecal peritonitis, glycosylated HBP treatment rescues mice from and an otherwise lethal injury. It appears that ng-HBP have significant effect on survival, and it can be concluded that ng-HBP can stimulate the host defence machinery albeit to a lesser extent than glycosylated HBP.

Animals↗
PubMed2005

Comparison of structural response and fatigue endurance of aircraft flap-like box structures subjected to acoustic loading.

The results of an extensive test program to characterize the behavior of typical aircraft structures under acoustic loading and to establish their fatigue endurance are presented. The structures tested were the three flap-like box-type of structures. Each structure consisted of one flat (bottom) and one curved (top) stiffener stiffened skin panel, front, and rear spars, and ribs that divided the structures into three bays. The three structures, constructed from three different materials (aircraft standard aluminum alloy, Carbon Fibre Reinforced Plastic, and a Glass Fibre Metal Laminate, i.e., GLARE) had the same size and configuration, with only minor differences due to the use of different materials. A first set of acoustic tests with excitations of intensity ranging from 140 to 160 dB were carried out to obtain detailed data on the dynamic response of the three structures. The FE analysis of the structures is also briefly described and the results compared with the experimental data. The fatigue endurance of the structures was then determined using random acoustic excitation with an overall sound pressure level of 161 dB, and details of crack propagation are reported.

Acoustics↗
PubMed2002

Smoothing of pixelated finite element models of cancellous bone structures and the effect on the predicted structural properties of the bone.

Many areas of biomedical engineering involve the modelling of biological systems, often using data from medical scanning techniques such as computed microtomography (microCT), and the prediction of the mechanical properties of these systems via finite element models. These models, and also those produced from remodelling simulations on idealized bone structures, are inherently highly pixelated and therefore have a high degree of surface roughness. The purpose of this paper is to demonstrate that this surface roughness need not necessarily have an influence on the predicted properties of the object under examination. To demonstrate this, two-dimensional idealized models of cancellous bone structures were used that were initially depleted and then rebuilt stochastically. A hysteresis effect was observed such that a significant amount of rebuilding beyond the original density was required to regain the initial intact stiffness. To ensure that this effect was not an artefact of the high degree of surface roughness of the rebuilt structures, a two-stage smoothing procedure was applied to assess if this had any effect on the stiffness of the structures. The superpixelation of the structures appeared to have a more profound effect than the smoothing procedures, although the smoothed structures still had stiffness and density values similar to those of the original structures, with a hysteresis effect still evident. This proves that the pixelization of the structures does not have a significant effect on the predicted mechanical properties of the structures. This work has important implications for other models that exhibit a high degree of surface roughness.

Artifacts↗
PubMed2000

Structural features of N-glycans linked to royal jelly glycoproteins: structures of high-mannose type, hybrid type, and biantennary type glycans.

The structures of N-glycans of total glycoproteins in royal jelly have been explored to clarify whether antigenic N-glycans occur in the famous health food. The structural feature of N-glycans linked to glycoproteins in royal jelly was first characterized by immunoblotting with an antiserum against plant complex type N-glycan and lectin-blotting with Con A and WGA. For the detail structural analysis of such N-glycans, the pyridylaminated (PA-) N-glycans were prepared from hydrazinolysates of total glycoproteins in royal jelly and each PA-sugar chain was purified by reverse-phase HPLC and size-fractionation HPLC. Each structure of the PA-sugar chains purified was identified by the combination of two-dimensional PA-sugar chain mapping, ESI-MS and MS/MS analyses, sequential exoglycosidase digestions, and 500 MHz 1H-NMR spectrometry. The immunoblotting and lectinblotting analyses preliminarily suggested the absence of antigenic N-glycan bearing beta1-2 xylosyl and/or alpha1-3 fucosyl residue(s) and occurrence of beta1-4GlcNAc residue in the insect glycoproteins. The detailed structural analysis of N-glycans of total royal jelly glycoproteins revealed that the antigenic N-glycans do not occur but the typical high mannose-type structure (Man(9 to approximately 4)GlcNAc2) occupies 71.6% of total N-glycan, biantennary-type structures (GlcNAc2Man3 GlcNAc2) 8.4%, and hybrid type structure (GlcNAc1 Man4GlcNAc2) 3.0%. Although the complete structures of the remaining 17% N-glycans; C4, (HexNAc3 Hex3HexNAc2: 3.0%), D2 (HexNAc2Hex5HexNAc2: 4.5%), and D3 (HexNAc3Hex4HexNAc2: 9.5%) are still obscure so far, ESI-MS analysis, exoglycosidase digestions by two kinds of beta-N-acetylglucosaminidase, and WGA blotting suggested that these N-glycans might bear a beta1-4 linkage N-acetylglucosaminyl residue.

Blotting, Western↗
PubMed2000

[The study of chromatin and chromosome structure on preparations of interphase nucleus derivatives resulting from nuclear wall removal. IV. Structural heterogeneity of stretched chromatin in membrane-free cell nuclei from human peripheral lymphocytes].

Densely aggregated chromatin of mature human or animal peripheral lymphocytes is inaccessible for structural investigation on preparations of both intact cell and conventionally spread chromatin. Giemsa- and DAPI-positive "free chromatin" structures, in addition to amembraneous nuclei, were isolated from intact lymphocytes gently treated with Triton-X-100. Surface stretching of both these nuclei and structures, shortly fixed in methanol-glacial acetic acid (3:1), revealed three main types of these "free chromatin" structures: dense chromatin structures (DCS), loose chromatin structures (LCS) and nuclear spreads (NS). The share of each nuclear derivative may be shifted by changing either detergent concentration and(or) the time of incubation in detergent solution. Each DSC consists of condensed "residual" nucleus, similar in from and size with an intact lymphocyte nucleus, and involves 1-15 uni- or olygonemic chromatin sprouts of different length. LSC contain heterogeneously loosened spindle-shape or drop-like nuclei, being several times longer and wider than DCS-nuclei, and 1-3 long uni- or olygonemic chromatin tail-pieces and incidentally observed lateral chromatin sprouts. The majority of LCS contain either a chromocenter of different number of end-to-end associated spindle-shape domains of condensed chromatin. The latter reached 2-5 x 1.5 microns being cross-striated or spiral in structure. NS represent spread chromatin fibrillar structures varying from 150 to 500 microns in length and from 1.5 to almost 50 microns in width. NS consist of 0.3-0.4 micron smooth and 0.4-0.8 micron beaded chromatin fibres. Thin fibres produce web-like domains of NS. and thick fibres form olygonemic bundles or end-to-end association of unit chromatin fibres within NS. Some portion of thick unit fibres of NS gave rise to local splitting into two thin fibres with a similar bead patterns. Thick argyrophilic fibers of the nucleolus also displayed a beaded structure and commonly spread hand-in-hand with the basic chromatin fibre aggregations.

Cell Nucleus↗
PubMed1994

Protein structural similarities predicted by a sequence-structure compatibility method.

A method for protein structure prediction has been developed, which evaluates the compatibility of an amino acid sequence with known 3-dimensional structures and identifies the most likely structure. The method was applied to a large number of sequences in a database, and the structures of the following proteins were predicted: (1) shikimate kinase (SKase), (2) the hydrophilic subunit of mannose permease (IIABMan), (3) rat tyrosine aminotransferase (Tyr AT), and (4) threonine dehydratase (TDH). The functional and evolutionary implications of the predictions are discussed. (1) The structural similarity between SKase and adenylate kinase was predicted. Alignment of their sequences reveals that the ATP-binding type A sequence motif and 2 ATP-binding arginine residues are conserved. The prediction suggests a similarity in their functional mechanisms as well as an evolutionary relationship. (2) The structural similarity between IIABMan and galactose/glucose-binding protein (GGBP) was predicted. The IIA and IIB domains are aligned with the N- and C-terminal domains of GGBP, respectively. The 2 phosphorylated residues, His 10 and His 175, of IIABMan are threaded onto loops located in the substrate-binding cleft of GGBP. The prediction accounts for the phosphoryl transfer from His 10 to His 175, and to the sugar substrate. (3) The structural similarity between rat Tyr AT and Escherichia coli aspartate AT was predicted, as well as (4) the structural similarity between TDH and the tryptophan synthase beta subunit. Predictions (3) and (4) support the previous predictions based on observations of the functional similarities between the proteins.

Amino Acid Sequence↗
PubMed2001

Examination of possible structural constraints of MHC-binding peptides by assessment of their native structure within their source proteins.

Antigenic peptides bind to major histocompatibility complex (MHC) molecules as a prerequisite for their presentation to T cells. In this study, we investigate possible structural preferences of MHC-binding peptides by examining the conformation space defined by the structures of these peptides within their native source proteins. Comparison of the conformation space of the native structures of MHC-binding nonamers and a corresponding conformation space defined by a random set of nonamers showed no significant difference. This suggests that the environment of the MHC binding groove has evolved to bind peptides with essentially any "structural background." A slight tendency for an extended beta-conformation at positions 8 and 9 was observed for the set of native structures. We suggest that such a preference may facilitate the binding of the C-terminal anchor position of processed peptides into the corresponding specificity pocket. MHC-binding peptides represent examples of short subsequences that are present in two different structural environments: within their native protein and within the MHC binding groove. Comparison of the native and of the bound structure of the peptides showed that peptides up to 14 residues long may adopt different conformations within different protein environments. This has direct implications for structure prediction algorithms.

Amino Acid Sequence↗
PubMed2005

Computation of conformational entropy from protein sequences using the machine-learning method--application to the study of the relationship between structural conservation and local structural stability.

A complete protein sequence can usually determine a unique conformation; however, the situation is different for shorter subsequences--some of them are able to adopt unique conformations, independent of context; while others assume diverse conformations in different contexts. The conformations of subsequences are determined by the interplay between local and nonlocal interactions. A quantitative measure of such structural conservation or variability will be useful in the understanding of the sequence-structure relationship. In this report, we developed an approach using the support vector machine method to compute the conformational variability directly from sequences, which is referred to as the sequence structural entropy. As a practical application, we studied the relationship between sequence structural entropy and the hydrogen exchange for a set of well-studied proteins. We found that the slowest exchange cores usually comprise amino acids of the lowest sequence structural entropy. Our results indicate that structural conservation is closely related to the local structural stability. This relationship may have interesting implications in the protein folding processes, and may be useful in the study of the sequence-structure relationship.

Amino Acid Sequence↗
PubMed1995

Solution structure of (Cd2+)1-calbindin D9k reveals details of the stepwise structural changes along the Apo-->(Ca2+)II1-->(Ca2+)I,II2 binding pathway.

The three-dimensional solution structure of (Cd2+)1-calbindin D9k has been determined by distance geometry, restrained molecular dynamics and relaxation matrix calculations using experimental constraints obtained from two-dimensional 1H and 15N-1H NMR spectroscopy. The final input data consisted of 1055 NOE distance constraints and 71 dihedral angle constraints, corresponding to 15 constraints per residue on average. The resulting ensemble of 24 structures has no distance or dihedral angle constraints consistently violated by more than 0.07 A and 1.8 degrees, respectively. The structure is characteristic of an EF-hand protein, with two helix-loop-helix calcium binding motifs joined by a flexible linker, and a short anti-parallel beta-type interaction between the two ion-binding sites. The four helices are well defined with a root mean square deviation from the mean coordinates of 0.35 A for the backbone atoms. The structure of the half-saturated cadmium state was compared with the previously determined solution structures of the apo and fully calcium saturated calbindin D9k. The comparisons were aided by introducing the ensemble averaged distance difference matrix as a tool for analyzing differences between two ensembles of structures. Detailed analyses of differences between the three states in backbone and side-chain dihedral angles, hydrogen bonds, interatomic distances, and packing of the hydrophobic core reveal the reorganization of the protein that occurs upon ion binding. Overall, it was found that (Cd2+)1-calbindin D9k, representing the half-saturated calcium state with an ion in site II, is structurally more similar to the fully calcium-saturated state than the apo state. Thus, for the binding sequence apo-->(Ca2+)II1-->(Ca2+)I,II2, the structural changes occurring upon ion binding are most pronounced for the first binding step, an observation that bears significantly on the molecular basis for cooperative calcium binding in calbindin D9k.

Animals↗
PubMed1997

The crystal structure of an Fe-superoxide dismutase from the hyperthermophile Aquifex pyrophilus at 1.9 A resolution: structural basis for thermostability.

Superoxide dismutase (SOD) from Aquifex pyrophilus, a hyperthermophilic bacterium, is an extremely heat-stable enzyme that maintains about 70% of its activity after heat treatment for 60 minutes at 100 degrees C. To understand the molecular basis of thermostability of this enzyme, we have determined the crystal structure of A. pyrophilus superoxide dismutase (Ap SOD), an Fe containing homotetrameric enzyme, at 1.9 A resolution, and compared it with SOD structures from a mesophile and a thermophile, and other enzyme structures from other hyperthermophiles. The structure has been refined to a crystallographic R-factor (I > 2sigma) of 17.0% and R-free (I > 2sigma) of 19.9%. While the overall structure of the Ap SOD monomer is similar to the other SODs, significant conformational differences are observed in a highly variable loop region and the C-terminal helix. The conformational differences in these regions alter the subunit arrangement of this enzyme and generate a very compact tetramer. Structural comparisons of three SODs have revealed that Ap SOD has some stabilizing features at both the tertiary and the quaternary structural level: The Ap SOD monomer contains a large number of ion-pairs and the Ap SOD tetramer has a dramatically increased buried surface area per monomer. Comparisons of the Ap SOD structure with that of other known enzymes from hyperthermophiles reveal that the increased number of intrasubunit ion-pairs is a common feature.

Amino Acid Sequence↗
PubMed2005

The automatic detection of known beta-propeller structural motifs from protein tertiary structure.

Following our previous work on the analysis of 'structural plasticity' associated with the beta-propeller structural motifs, we have now developed a simple method that can automatically detect all the known beta-propellers in protein tertiary structure, given a list of Protein Data Bank (PDB) codes as input to the computer program. Our beta-propeller detection (BPD) method identifies the location of beta-propellers in the protein structure, specifies the beta-propeller type, the beta-sheet associated beta-strand pattern and the structurally similar beta-propellers observed in other proteins. When tested on 21,566 proteins in the PDB, the BPD method was capable of correctly identifying all the known 245 beta-propellers described in the structural classification of proteins (SCOP) with the number of false positives detected being less than 0.2%. Forty-one false positives were detected that correspond to eight known protein families. When compared with some of the popular web-based programs that can automatically detect 'structural similarities' between the query and target proteins, our method has the advantage of also being capable of detecting beta-propellers associated with 'structural plasticity' and in situations where the target and query proteins differ in amino acid sequence length.

Amino Acid Motifs↗
PubMed1994

High resolution structures of the 4-4-20 Fab-fluorescein complex in two solvent systems: effects of solvent on structure and antigen-binding affinity.

Three-dimensional structures were determined for three crystal forms of the antigen binding fragment (Fab) of anti-fluorescein antibody 4-4-20 in complex with fluorescein. These included 1) a triclinic (P1) form crystallized in 47% (v/v) 2-methyl-2,4-pentanediol (MPD); 2) a triclinic (P1) form crystallized in 16% (w/v) poly(ethylene glycol), molecular weight 3350 (PEG); and 3) a monoclinic (P21) form crystallized in 16% PEG. Solvent molecules were added to the three models and the structures were refined to their diffraction limits (1.75-A, 1.78-A, and 2.49-A resolution for the MPD, triclinic PEG, and monoclinic PEG forms, respectively). Comparisons of these structures were interesting because 4-4-20 exhibited a lower antigen-binding affinity in 47% MPD (Ka = 1.3 x 10(8) M-1) than in either 16% PEG (Ka = 2.9 x 10(9) M-1) or phosphate-buffered saline (Ka = 1.8 x 10(10) M-1). Even though the solution behavior of the antibody was significantly different in MPD and PEG, the crystal structures were remarkably similar. In all three structures, the fluorescein-combining site was an aromatic slot formed by tyrosines L32, H96, and H97 and tryptophans L96 and H33. In addition, several active site constituents formed an electrostatic network with the ligand. These included a salt link between arginine L34 and one of fluorescein's enolate oxygen atoms, a hydrogen bond between histidine L27d and the second enolic group, a hydrogen bond between tyrosine L32 and the phenylcarboxylate group, and two medium range (approximately 5 A) electrostatic interactions with lysine L50 and arginine H52. The only major difference between the triclinic MPD and PEG structures was the degree of hydration of the antigen-combining site. Three water molecules participated in the above electrostatic network in the MPD structure, while eight were involved in the PEG structure. Based on this observation, we believe that 4-4-20 exhibits a lower affinity in MPD due to the depletion of the hydration shell of the antigen-combining site.

Amino Acid Sequence↗
PubMed1995

Determination of the three-dimensional solution structure of noxiustoxin: analysis of structural differences with related short-chain scorpion toxins.

The 3D structure of noxiustoxin, the first identified scorpion toxin acting on K+ channels, has been elucidated by NMR and molecular modeling. Thirty-nine solution structures were calculated using 572 distance and 42 dihedral restraints. The average atomic rms deviation between the refined structures and the mean structure is 0.75 A for the backbone atoms. Noxiustoxin adopts a alpha/beta scaffold constituted of a three-stranded beta-sheet (residues 2-3, 25-30, 33-38) linked to a helix (residues 10-20) through two disulfide bridges. A comparison between the 3D structure of noxiustoxin and those of other structurally and functionally related scorpion toxins (charybdotoxin, PO5-NH2, kaliotoxin) revealed a bending capacity of the helix and a variability in the relative orientations between the helix and the beta-sheet. These two features highlight the plasticity of the alpha/beta scaffold and offer a structural explanation for the capacity of the fold to accommodate an additional alanine residue in the Gly-x-Cys pattern of a previously proposed consensus sequence [Bontems et al. (1991) Science 254, 1521-1523]. Our structural data also emphasize the possibility that the beta-sheet of NTX is implicated in the capacity of NTX to recognize voltage-dependent K+ channels.

Amino Acid Sequence↗
PubMed1994

Sequence specificity of quinoxaline antibiotics. 1. Solution structure of a 1:1 complex between triostin A and [d(GACGTC)]2 and comparison with the solution structure of the [N-MeCys3,N-MeCys7]TANDEM-[d(GATATC)]2 complex.

Triostin A, a naturally occurring quinoxaline antibiotic that contains N-methyl groups on the valine and cysteine residues, binds sequence specifically to DNA at NCGN sites. [N-MeCys3,N-MeCys7]-TANDEM (CysMeTANDEM), a synthetic quinoxaline antibiotic, differs in its chemical structure from triostin A only at the valine residues, which contain no N-methyl substituents. CysMeTANDEM has a sequence specificity different from triostin A, binding specifically to DNA at NTAN sites. To understand the factors that determine the sequence specificity of these quinoxaline antibiotics, the solution structure of a 1:1 complex of triostin A with the DNA hexamer [d(GACGTC)]2 has been determined using NMR-derived distance and dihedral angle restraints. The solution structure of the triostin A-[d(GACGTC)]2 complex is compared directly to the solution structure of a 1:1 complex of CysMeTANDEM with [d(GATATC)]2 and is also compared to the crystal structure of 2:1 complex of triostin A with [d(CGTACG)]2. Triostin A binds to [d(GACGTC)]2 as a bis-intercalator around the CpG step, and the peptide ring of the drug binds in the minor groove of the DNA. The central C.G base pairs of the complex are underwound with an average helical twist angle of approximately -9.0 degrees and buckle inward by about 25 degrees. There are intermolecular hydrogen bonds between each of the Ala NH and the GN3 protons of the CpG binding site. Similar structural features are observed in the solution structure of the CysMeTANDEM-[d(GATATC)]2 complex. However, in the structure of the triostin A-[d(GACGTC)]2 complex, two intermolecular hydrogen bonds between each of the Ala CO oxygens of the drug and the 2-amino protons of guanine are observed. These hydrogen bonds do not form in the CysMeTANDEM-DNA complex. Instead, CysMeTANDEM contains two intramolecular hydrogen bonds between the Ala CO atoms and the Val amide protons, making the Ala CO atoms unavailable to form two intermolecular hydrogen bonds. The role of these intermolecular hydrogen bonds in the CpG specificity of triostin A is discussed.

Anti-Bacterial Agents↗
PubMedDate not supplied

Distribution analysis of the variation of B-factors of X-ray crystal structures; temperature and structural variations in lysozyme.

The B-factor (isotropic temperature factor) data for X-ray structures of hen egg-white lysozyme from the study of Young et al. (Young, Dewan, Nave, and Tilton J. Appl. Cryst. 1993, 26, 309-319) potentially contain information about the relative contributions of static and dynamic variation to these factors. The six structures of the protein were obtained at two widely different temperatures (100 and 298 K), with two crystal forms (monoclinic and tetragonal) and other experimental differences. In addition, the monoclinic lysozyme crystals with two molecules per asymmetric unit allow direct examination of variation between structures determined under identical conditions at both temperatures. The B-factors from these structures all have complex distribution functions as might be expected considering all of the influences that these values must reflect. The empirical cumulative distribution functions (eCDF's) of these data show that they are representative of complex, multicomponent distributions. Distribution analysis using the DANFIP procedure (Wampler, Anal. Biochemistry 1990, 186, 209-218) of the data sets reveals that they can be modeled as four to six Gaussian subpopulations, that these subpopulations do not correlate with specific atom types, specific amino acid residues or fixed locations in the structure. While they do seem to correlate with localized groupings of atoms, these grouping vary from structure to structure even within the same crystal under the same conditions. Temperature seems to have a global effect in this case, but it is clear that other factors including experimental error influence the distribution of B-factors within a given structure. This analysis also helps explain the oft observed lack of atomic level correlation between experimental B-factors and calculated mean square displacements from molecular dynamics simulations.

Algorithms↗
PubMed2002

A new B-chain mutant of insulin: comparison with the insulin crystal structure and role of sulfonate groups in the B-chain structure.

The solution structure of a new B-chain mutant of bovine insulin, in which the cysteines B7 and B19 are replaced by two serines, has been determined by circular dichroism, 2D-NMR and molecular modeling. This structure is compared with that of the oxidized B-chain of bovine insulin [Hawkins et al. (1995) Int. J. Peptide Protein Res.46, 424-433]. Circular dichroism spectroscopy showed in particular that a higher percentage of helical secondary structure for the B-chain mutant is estimated in trifluoroethanol solution in comparison with the oxidized B-chain. 2D-NMR experiments confirmed, among multiple conformations, that the B-chain mutant presents defined secondary structures such as a alpha-helix between residues B9 and B19, and a beta-turn between amino acids B20 and B23 in aqueous trifluoroethanol. The 3D structures, which are consistent with NMR data and were obtained using a simulated annealing protocol, showed that the tertiary structure of the B-chain mutant is better resolved and is more in agreement with the insulin crystal structure than the oxidized B-chain structure described by Hawkins et al. An explanation could be the presence of two sulfonate groups in the oxidized insulin B-chain. Either by their charges and/or their size, such chemical groups could play a destructuring effect and thus could favor peptide flexibility and conformational averaging. Thus, this study provides new insights on the folding of isolated B-chains.

Amino Acid Sequence↗
PubMed1995

Protein structure prediction: recognition of primary, secondary, and tertiary structural features from amino acid sequence.

This review attempts a critical stock-taking of the current state of the science aimed at predicting structural features of proteins from their amino acid sequences. At the primary structure level, methods are considered for detection of remotely related sequences and for recognizing amino acid patterns to predict posttranslational modifications and binding sites. The techniques involving secondary structural features include prediction of secondary structure, membrane-spanning regions, and secondary structural class. At the tertiary structural level, methods for threading a sequence into a mainchain fold, homology modeling and assigning sequences to protein families with similar folds are discussed. A literature analysis suggests that, to date, threading techniques are not able to show their superiority over sequence pattern recognition methods. Recent progress in the state of ab initio structure calculation is reviewed in detail. The analysis shows that many structural features can be predicted from the amino acid sequence much better than just a few years ago and with attendant utility in experimental research. Best prediction can be achieved for new protein sequences that can be assigned to well-studied protein families. For single sequences without homologues, the folding problem has not yet been solved.

Amino Acid Sequence↗