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At least 1,171 records · Page 65Linked to original sources
PubMed1995

Tertiary structure of [2Fe-2S] ferredoxin from Spirulina platensis refined at 2.5 A resolution: structural comparisons of plant-type ferredoxins and an electrostatic potential analysis.

The structure of plant-type [2Fe-2S] ferredoxin isolated from Spirulina platensis has been refined using diffraction data to 2.5 A resolution by alternate cycles of simulated annealing and manual revision of the model. The final R factor is 19.9% for 2,912 reflections with F > 2 sigma F between 8.0 and 2.5 A resolution. S. platensis ferredoxin, like other plant-type [2Fe-2S] ferredoxins, has a major alpha-helix flanking a sheet consisting of four beta strands. The present refinement revises the conformation of residues 56-71, in which a one-turn helix was identified. Superposition of the Spirulina ferredoxin structure on the structures of other ferredoxins that have been well refined showed structural perturbation at a few residues on the amino and carboxyl termini and the turn between the first and second beta-strands. The root-mean-square deviations of the corresponding C alpha atoms of the pairs of ferredoxins range from 0.90 to 1.17 A for all the residues, but from 0.64 to 0.70 A if the few perturbed residues are excluded. Therefore, it may be concluded that the main-chain foldings of all the plant-type [2Fe-2S] ferredoxins are essentially the same. Electrostatic potential analysis showed that the molecular surface around the cluster is negatively charged, whereas that of the beta-sheet of the other side is positively charged. The interaction between ferredoxin and ferredoxin-NADP+ reductase is discussed on the basis of the charge distributions of these molecules and biochemical data.

Amino Acid Sequence↗
PubMed1998

Protein secondary structure prediction in different structural classes.

Information about the secondary structure of a protein can be helpful in understanding its native folded state. In previous work, it was shown that the medium-range interactions predominate in all-alpha class and the long-range interactions predominate in all-beta class proteins. Based on this, in this work the performance of several structure prediction methods in different structural classes of globular proteins was analyzed. It was found that all the methods predict the secondary structures of all-alpha proteins more accurately than other classes.

Protein Structure, Secondary↗
PubMed2000

The 2000 Olympic Games of protein structure prediction; fully automated programs are being evaluated vis-à-vis human teams in the protein structure prediction experiment CAFASP2.

In this commentary, we describe two new protein structure prediction experiments being run in parallel with the CASP experiment, which together may be regarded as the 2000 Olympic Games of structure prediction. The first new experiment is CAFASP, the Critical Assessment of Fully Automated Structure Prediction. In CAFASP, the participants are fully automated programs or Internet servers, and here the automated results of the programs are evaluated, without any human intervention. The second new experiment, named LiveBench, follows the CAFASP ideology in that it is aimed towards the evaluation of automatic servers only, while it runs on a large set of prediction targets and in a continuous fashion. Researchers will be watching the 2000 protein structure prediction Olympic Games, to be held in December, in order to learn about the advances in the classical 'human-plus-machine' CASP category, the fully automated CAFASP category, and the comparison between the two.

Amino Acid Sequence↗
PubMed1995

Flavoprotein structure and mechanism. 5. Trypanothione reductase and lipoamide dehydrogenase as targets for a structure-based drug design.

Trypanothione reductase (TR) is a flavoenzyme that has been found only in parasitic protozoa of the order Kinetoplastida. The enzyme catalyzes the NADPH-dependent reduction of glutathionylspermidine conjugates and is a key enzyme of the parasite's thiol metabolism. Consequently, TR is an attractive target molecule for a structure-based drug development against Chagas' disease, African sleeping sickness, and other diseases caused by trypanosomes and leishmanias. The three-dimensional structures of TR and of three enzyme substrate complexes have been solved. Several classes of compounds are discussed as guide structures for the design of specific inhibitors. Among them are tricyclic compounds such as acridines and phenothiazines, which competitively inhibit TR but not the related host enzyme glutathione reductase, as well as oxidase activity-inducing quinones and nitrofurans. Lipoamide dehydrogenase (LipDH) is another flavoprotein discussed as a target molecule for an antitrypanosomal therapy. In Trypanosoma cruzi, an organism that is highly susceptible to oxidative stress, LipDH participates in the redox cycling of nifurtimox, one of the most effective anti-Chagas agents. In conclusion, the structurally related enzymes TR and LipDH exhibit an unusually high one-electron-reducing capacity. Consequently, turncoat inhibitors and other compounds inducing an oxidase activity in both enzymes are promising drug candidates against Chagas' disease.

Animals↗
PubMed2026

Hidden genomic structure and widespread structural polymorphism across environmental gradients in the spiny sea star Marthasterias glacialis.

Genomic regions of reduced recombination can preserve linkage among co-adapted alleles, facilitating local adaptation despite high connectivity. Such regions-often generated by chromosomal inversions-may be especially important in highly dispersive marine taxa yet remain poorly documented in echinoderms. Here, we combined a chromosome-level reference genome with genome-wide ddRAD-seq from 296 Marthasterias glacialis individuals across 19 Atlantic-Mediterranean locations to quantify population structure and scan for recombination-suppressed haploblocks. Genome-wide neutral markers showed significant population differentiation together with evidence of high connectivity, revealed by the presence of inter-ecoregion migrants. Additionally, we identified 16 polymorphic haploblocks with patterns consistent with putative chromosomal inversions spanning 18.6% of the genome. Haploblock haplotypes were strongly environmentally and geographically structured and contained genes with key functions in stress response, osmoregulation and thermal tolerance. Haplotype distributions also paralleled previously described mitochondrial lineages despite nuclear gene flow, consistent with a model of ancient divergence followed by secondary contact. Overall, our results suggest a role for widespread structural polymorphism in adaptive differentiation in Echinodermata, providing a framework for linking echinoderm genome rearrangements to ecological divergence. Marthasterias glacialis thus emerges as a promising system to explore how structural variation contributes to adaptation and genome evolution in highly dispersive organisms.

Animals↗
PubMed1997

Hypothesis on particle structure and assembly of rice dwarf phytoreovirus: interactions among multiple structural proteins.

To study the morphogenesis and packaging of rice dwarf phytoreovirus (RDV), the interactions among multiple structural proteins were analysed using both the yeast two-hybrid system and far-Western blotting analysis. The following protein-protein interactions were observed. P3 (major core protein) bound to itself as well as to P7 (nucleic acid-binding protein) and P8 (major outer capsid protein). P7 bound to P1 (RNA-dependent RNA polymerase) and P8, in addition to P3. Based on these findings, we hypothesize that the core shell structure is based on P3-P3 interactions and that P7 has the ability to bind to multiple structural proteins as well as to genomic RNAs during viral particle assembly. Based on the observed protein-protein interactions and on computer-aided analysis of the numbers of structural proteins per particle, possible RDV assembly events are proposed.

Models, Molecular↗
PubMed1990

Structural comparison of the potent antimuscarinic agent azaprophen hydrochloride with aprophen hydrochloride and structurally related antimuscarinic agents.

A comparison of the crystalline structure of the potent azaprophen with the crystalline structures of aprophen and four other structurally related antimuscarinic agents reveals the potential for an ionic interaction of the cationic nitrogen atom and the carbonyl oxygen atom with the muscarinic receptor and an aromatic interaction with a phenyl group. 6-Methyl-6-azabicyclo[3.2.1]octan-3 alpha-ol 2,2-diphenylpropionate hydrochloride (azaprophen hydrochloride), C23H28NO2+.Cl-, Mr = 385.9, monoclinic, P2(1)/c, a = 8.490 (1), b = 14.335 (2), c = 16.847 (2) A, beta = 93.63 (1) degree, V = 2046.2 A3, Z = 4, Dx = 1.253 g cm-3, Cu K alpha, lambda = 1.54178 A, mu = 17.86 cm-1, F(000) = 824, room temperature, final R = 4.25% for 2460 reflections with [Fo[ greater than 3 sigma. 2-Diethylaminoethyl 2,2-diphenylpropionate hydrochloride (aprophen hydrochloride), C21H28NO2+.Cl-, Mr = 361.9, orthorhombic, Pbca, a = 15.118 (3), b = 7.488 (2), c = 36.306 (10) A, V = 4110.8 A3, Z = 8, Dx = 1.316 g cm-3, Cu K alpha, lambda = 1.54178 A, mu = 17.45 cm-1, F(000) = 1552, room temperature, final R = 7.96% for 1846 reflections with [Fo[ greater than 3 sigma. Both azaprophen and aprophen were crystallized as tertiary amine salts. The overall conformation of both molecules is similar as demonstrated by space-filling models and superimposed stick drawings. Although the interatomic distance between the nitrogen atom and the carbonyl oxygen atom of azaprophen and aprophen is comparable at 5.41 and 5.07 A, respectively, the nitrogen atoms of azaprophen and aprophen are 1.16 A apart when the acyloxy portion (--O--C = O) of both molecules is superimposed. A conformational analysis of azaprophen, aprophen and the structurally similar antimuscarinic agents reveals a buried ether oxygen atom and an exposed carbonyl oxygen atom as well as the common placement of a phenyl group on the same side of the acyloxy plane as the cationic nitrogen atom.(ABSTRACT TRUNCATED AT 250 WORDS)

Models, Molecular↗
PubMed1994

Structure of 1,1,5,5-tetranitro-[4]peristylane. Structure solution from molecular packing analysis.

The structure of the title compound, decahydro-2,2,5,5-tetranitro-1,6:3,4-dimethanocyclobuta[1,2: 3, 4]dicyclopentene, C12H12N4O8, was solved with the molecular packing program MOLPAK, starting with an AM1-geometry-optimized model of an isolated molecule. The 20 best predicted crystal structures from the MOLPAK procedure were subjected to lattice energy refinement with the WMIN program. A structure-factor calculation with the top MOLPAK/WMIN derived structure and the 197 Fo data to sin theta/lambda = 0.324 A-1 (theta = 30 degrees) gave an R value of 0.29. Final R = 0.057, wR = 0.067 for 730 reflections with I > 3 sigma (I). There are no unusual intermolecular distances and crystal packing is normal.

Bridged-Ring Compounds↗
PubMed2002

Domain closure and action of uracil DNA glycosylase (UDG): structures of new crystal forms containing the Escherichia coli enzyme and a comparative study of the known structures involving UDG.

The structures of a new crystal form of free Escherichia coli uracil DNA glycosylase (UDG), containing four molecules in the asymmetric unit, and two forms of its complex with the proteinaceous inhibitor Ugi, containing two and four crystallographically independent complexes, have been determined. A comparison of these structures and the already known crystal structures containing UDG shows that the enzyme can be considered to be made up of two independently moving structural entities or domains. A detailed study of free and DNA-bound human enzyme strengthens this conclusion. The domains close upon binding to uracil-containing DNA, whereas they do not appear to do so upon binding to Ugi. The comparative study also shows that the mobility of the molecule involves the rigid-body movement of the domains superposed on flexibility within domains.

Crystallography, X-Ray↗
PubMed2004

Structure of circularly permuted DsbA(Q100T99): preserved global fold and local structural adjustments.

The thiol-disulfide oxidoreductase DsbA is required for efficient formation of disulfide bonds in the Escherichia coli periplasm. The enzyme is the strongest oxidant of the family of thioredoxin-like proteins and three-dimensional structures of both oxidized and reduced forms are known. DsbA consists of a catalytic thioredoxin-like domain and a helical domain that is inserted into the thioredoxin motif. Here, the X-ray structure of a circularly permuted variant, cpDsbA(Q100T99), is reported in which the natural termini are joined by the pentapeptide linker GGGTG, leading to a continuous thioredoxin domain, and new termini that have been introduced in the helical domain by breaking the peptide bond Thr99-Gln100. cpDsbA(Q100T99) is catalytically active in vivo and in vitro. The crystal structure of oxidized cpDsbA(Q100T99), determined by molecular replacement at 2.4 A resolution, was found to be very similar to that of wild-type DsbA. The lower thermodynamic stability of cpDsbA(Q100T99) relative to DsbA is associated with small structural changes within the molecule, especially near the new termini and the circularizing linker. The active-site helices and adjacent loops display increased flexibility compared with oxidized DsbA.

Amino Acid Motifs↗
PubMed2000

The molecular structure and structural transition of the alpha-helical capsid in filamentous bacteriophage Pf1.

The major coat protein in the capsid of Pf1 filamentous bacteriophage (Inovirus) forms a helical assembly of about 7000 identical protein subunits, each of which contains 46 amino-acid residues and can be closely approximated by a single gently curved alpha-helix. Since the viral DNA occupies the core of the tubular capsid and appears to make no significant specific interactions with the capsid proteins, the capsid is a simple model system for the study of the static and dynamic properties of alpha-helix assembly. The capsid undergoes a reversible temperature-induced structural transition at about 283 K between two slightly different helix forms. The two forms can coexist without an intermediate state, consistent with a first-order structural phase transition. The molecular model of the higher temperature form was refined using improved X-ray fibre diffraction data and new refinement and validation methods. The refinement indicates that the two forms are related by a change in the orientation of the capsid subunits within the virion, without a significant change in local conformation of the subunits. On the higher temperature diffraction pattern there is a region of observed intensity that is not consistent with a simple helix of identical subunits; it is proposed that the structure involves groups of three subunits which each have a slightly different orientation within the group. The grouping of subunits suggests that a change in subunit libration frequency could be the basis of the Pf1 structural transition; calculations from the model are used to explore this idea.

Amino Acid Sequence↗
PubMed2002

A structure for the yeast prohibitin complex: Structure prediction and evidence from chemical crosslinking and mass spectrometry.

The mitochondrial prohibitin complex consists of two subunits (PHB1 of 32 kD and PHB2 of 34 kD), assembled into a membrane-associated supercomplex of approximately 1 MD. A chaperone-like function in holding and assembling newly synthesized mitochondrial polypeptide chains has been proposed. To further elucidate the function of this complex, structural information is necessary. In this study we use chemical crosslinking, connecting lysine side chains, which are well scattered along the sequence. Crosslinked peptides from protease digested prohibitin complexes were identified with mass spectrometry. From these results, spatial restraints for possible protein conformation were obtained. Many interaction sites between PHB1 and PHB2 were found, whereas no homodimeric interactions were observed. Secondary and tertiary structural predictions were made using several algorithms and the models best fitting the spatial restraints were selected for further evaluation. From the structure predictions and the crosslink data we derived a structural building block of one PHB1 and one PHB2 subunit, strongly intertwined along most of their length. The size of the complex implies that approximately 14 of these building blocks are present. Each unit contains a putative transmembrane helix in PHB2. Taken together with the unit building block we postulate a circular palisade-like arrangement of the building blocks projecting into the intermembrane space.

Amino Acid Sequence↗
PubMed2003

The structure of Pseudomonas P51 Cl-muconate lactonizing enzyme: co-evolution of structure and dynamics with the dehalogenation function.

Bacterial muconate lactonizing enzymes (MLEs) catalyze the conversion of cis,cis-muconate as a part of the beta-ketoadipate pathway, and some MLEs are also able to dehalogenate chlorinated muconates (Cl-MLEs). The basis for the Cl-MLEs dehalogenating activity is still unclear. To further elucidate the differences between MLEs and Cl-MLEs, we have solved the structure of Pseudomonas P51 Cl-MLE at 1.95 A resolution. Comparison of Pseudomonas MLE and Cl-MLE structures reveals the presence of a large cavity in the Cl-MLEs. The cavity may be related to conformational changes on substrate binding in Cl-MLEs, at Gly52. Site-directed mutagenesis on Pseudomonas MLE core positions to the equivalent Cl-MLE residues showed that the variant Thr52Gly was rather inactive, whereas the Thr52Gly-Phe103Ser variant had regained part of the activity. These residues form a hydrogen bond in the Cl-MLEs. The Cl-MLE structure, as a result of the Thr-to-Gly change, is more flexible than MLE: As a mobile loop closes over the active site, a conformational change at Gly52 is observed in Cl-MLEs. The loose packing and structural motions in Cl-MLE may be required for the rotation of the lactone ring in the active site necessary for the dehalogenating activity of Cl-MLEs. Furthermore, we also suggest that differences in the active site mobile loop sequence between MLEs and Cl-MLEs result in lower active site polarity in Cl-MLEs, possibly affecting catalysis. These changes could result in slower product release from Cl-MLEs and make it a better enzyme for dehalogenation of substrate.

Amino Acid Sequence↗
PubMed2004

The structure of Ski8p, a protein regulating mRNA degradation: Implications for WD protein structure.

Ski8p is a 44-kD protein that primarily functions in the regulation of exosome-mediated, 3'--> 5' degradation of damaged mRNA. It does so by forming a complex with two partner proteins, Ski2p and Ski3p, which complete a complex that is capable of recruiting and activating the exosome/Ski7p complex that functions in RNA degradation. Ski8p also functions in meiotic recombination in complex with Spo11 in yeast. It is one of the many hundreds of primarily eukaryotic proteins containing tandem copies of WD repeats (also known as WD40 or beta-transducin repeats), which are short ~40 amino acid motifs, often terminating in a Trp-Asp dipeptide. Genomic analyses have demonstrated that WD repeats are found in 1%-2% of proteins in a typical eukaryote, but are extremely rare in prokaryotes. Almost all structurally characterized WD-repeat proteins are composed of seven such repeats and fold into seven-bladed beta propellers. Ski8p was thought to contain five WD repeats on the basis of primary sequence analysis implying a five-bladed propeller. The 1.9 A crystal structure unexpectedly exhibits a seven-bladed propeller fold with seven structurally authentic WD repeats. Structure-based sequence alignments show additional sequence diversity in the two undetected repeats. This demonstrates that many WD repeats have not yet been identified in sequences and also raises the possibility that the seven-bladed propeller may be the predominant fold for this family of proteins.

Amino Acid Motifs↗
PubMed2000

Structural similarities and differences in Staphylococcus aureus exfoliative toxins A and B as revealed by their crystal structures.

Staphylococcal aureus epidermolytic toxins (ETs) A and B are responsible for the induction of staphylococcal scalded skin syndrome, a disease of neonates and young children. The clinical features of this syndrome vary from localized blisters to severe exfoliation affecting most of the body surface. Comparison of the crystal structures of two subtypes of ETs-rETA (at 2.0 A resolution), rETB (at 2.8 A resolution), and an active site variant of rETA, Ser195Ala at 2.0 A resolution has demonstrated that their overall topology resembles that of a "trypsin-like" serine protease, but with significant differences at the N- and C-termini and loop regions. The details of the catalytic site in both ET structures are very similar to those in glutamate-specific serine proteases, suggesting a common catalytic mechanism. However, the "oxyanion hole," which is part of the catalytic sites of glutamate specific serine proteases, is in the closed or inactive conformation for rETA, yet in the open or active conformation for rETB. The ETs contain a unique amphipathic helix at the N-terminus, and it appears to be involved in optimizing the conformation of the catalytic site residues. Determination of the structure of the rETA catalytic site variant, Ser195Ala, showed no significant perturbation at the active site, establishing that the loss of biological and esterolytic activity can be attributed solely to disruption of the catalytic serine residue. Finally, the crystal structure of ETs, together with biochemical data and mutagenesis studies, strongly confirms the classification of these molecules as "serine proteases" rather than "superantigens."

Amino Acid Sequence↗
PubMed1996

Detection of the disease severity-related molecular differences among new Thai dengue-2 isolates in 1993, based on their structural proteins and major non-structural protein NS1 sequences.

We determined the nucleotide sequences of the whole structural protein gene of four new dengue-2 viruses by the primer extension dideoxy chain termination method, using multiple cDNA clones for six overlapping gene regions. The nucleotide sequences of the major non-structural protein NS1 gene of these viruses were also determined by direct sequencing of the reverse-transcription polymerase chain reaction products. These viruses were isolated from dengue patients with different clinical severities in Nakhon Phanom, Northeastern Thailand in 1993. The results were compared with the sequences of prototype New Guinea C strain and other reference strains. All four viruses revealed highest homology to New Guinea C strain. The homology between each of the four strains and New Guinea C strain varies from 95.09% to 95.29% in its nucleotide sequences, and from 97.24% to 97.78% in its amino acid sequences covering all structural proteins and NS1 protein. The PreM region shows the highest divergence (6.59% to 7.32%) in its nucleotide sequence, whereas C protein is most highly conserved (only 1.75% to 2.63% divergence). Our data showed that there are certain molecular differences in the genomic structure of these four new isolates, which indicate the possibility that these changes are related with the virulence of the virus strains.

Amino Acid Sequence↗
PubMed1980

Structure-staining relationships in histochemistry and biological staining. I. Theoretical background and a general account of correlation of histochemical staining with the chemical structure of the reagents used.

A description is given of the choice, rationale and calculation of several numerical coefficients for describing the chemical structures of staining reagents such as dyestuffs, enzyme substrates, diazonium and tetrazolium salts. Using such coefficients, structure-staining correlations may be made for many staining systems. Examples include the structural correlations of the quantitative affinity measurements of the staining of chromatin with basic dyes, the tetrazolium salts for use as visualizing agents in enzyme histochemistry, and the use of bis-azo compounds as acid or basic dyes, or as fat stains. The value of such structure-staining correlation models for assisting the rational selection and design of new histochemical reagents, and for understanding old reagents and procedures, is discussed.

Chemical Phenomena↗
PubMed1992

The primary structure of piscine (Oncorhynchus mykiss) retinol-binding protein and a comparison with the three-dimensional structure of mammalian retinol-binding protein.

1. The primary structures of two variants of rainbow trout (Oncorhynchus mykiss) plasma retinol-binding protein (RBP) were determined and found to be approximately 60% identical with those of both human and Xenopus laevis RBPs. The comparable sequence similarities that we have found agree with the estimate of similar divergence times between bony fishes and mammals and between bony fishes and amphibians. The two piscine RBP variants differ by six amino acid substitutions at positions that are not crucial for the interaction with retinol, on the basis of the human RBP three-dimensional structure [Cowan, S. W., Newcomer, M. E. & Jones, T. A. (1990) Proteins Struct. Func. Genet. 8, 44-61]. 2. Models were developed for the three-dimensional structures of rainbow trout and X. laevis RBPs, based on that of human RBP. The overall three-dimensional structure appears to be very well preserved for RBPs isolated from vertebrate species for which the divergence time is 350-400 million years. At variance with an almost absolute conservation for the residues that participate in the formation of the retinol binding site in mammalian RBPs, several amino acid replacements are found for this part of the RBP molecule when the comparison is extended to piscine and amphibian RBPs. However, the only allowed amino acid replacements are either conservative or more than 0.4 nm distant from retinol. Besides the retinol binding site, a few regions at the protein surface appear to be rather conserved during phylogenetic development of vertebrates and, therefore, might be involved in molecular interactions.

Amino Acid Sequence↗