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PubMed1998

Crystal structure of the phosphatidylethanolamine-binding protein from bovine brain: a novel structural class of phospholipid-binding proteins.

BACKGROUND: Phosphatidylethanolamine-binding protein (PEBP) is a basic protein found in numerous tissues from a wide range of species. The screening of gene and protein data banks defines a family of PEBP-related proteins that are present in a variety of organisms, including Drosophila and inferior eukaryotes. PEBP binds to phosphatidylethanolamine and nucleotides in vitro, but its biological function in vivo is not yet known. The expression of PEBP and related proteins seems to be correlated with development and cell morphogenesis, however. To obtain new insights into the PEBP family and its potential functions, we initiated a crystallographic study of bovine brain PEPB. RESULTS: The X-ray crystal structure of bovine brain PEBP has been solved using multiple isomorphous replacement methods, and refined to 1.84 A resolution. The structure displays a beta fold and exhibits one nonprolyl cis peptide bond. Analysis of cavities within the structure and sequence alignments were used to identify a putative ligand-binding site. This binding site is defined by residues of the C-terminal helix and the residues His85, Asp69, Gly109 and Tyr119. This site also corresponds to the binding site of phosphorylethanolamine, the polar head group of phosphatidylethanolamine. CONCLUSIONS: This study shows that PEBP is not related to the G-protein family nor to known lipid-binding proteins, and therefore defines a novel structural family of phospholipid-binding proteins. The PEBP structure contains no internal hydrophobic pocket, as described for lipocalins or small phospholipid-transfer proteins. Nevertheless, in PEBP, a small cavity close to the protein surface has a high affinity for anions, such as phosphate and acetate, and also phosphorylethanolamine. We suggest that this cavity corresponds to the binding site of the polar head group of phosphatidylethanolamine.

Amino Acid Sequence↗

PubMed2002

Ligatoxin B, a new cytotoxic protein with a novel helix-turn-helix DNA-binding domain from the mistletoe Phoradendron liga.

A new basic protein, designated ligatoxin B, containing 46 amino acid residues has been isolated from the mistletoe Phoradendron liga (Gill.) Eichl. (Viscaceae). The protein's primary structure, determined unambiguously using a combination of automated Edman degradation, trypsin enzymic digestion, and tandem MS analysis, was 1-KSCCPSTTAR-NIYNTCRLTG-ASRSVCASLS-GCKIISGSTC-DSGWNH-46. Ligatoxin B exhibited in vitro cytotoxic activities on the human lymphoma cell line U-937-GTB and the primary multidrug-resistant renal adenocarcinoma cell line ACHN, with IC50 values of 1.8 microM and 3.2 microM respectively. Sequence alignment with other thionins identified a new member of the class 3 thionins, ligatoxin B, which is similar to the earlier described ligatoxin A. As predicted by the method of homology modelling, ligatoxin B shares a three-dimensional structure with the viscotoxins and purothionins and so may have the same mode of cytotoxic action. The novel similarities observed by structural comparison of the helix-turn-helix (HTH) motifs of the thionins, including ligatoxin B, and the HTH DNA-binding proteins, led us to propose the working hypothesis that thionins represent a new group of DNA-binding proteins. This working hypothesis could be useful in further dissecting the molecular mechanisms of thionin cytotoxicity and of thionin opposition to multidrug resistance, and useful in clarifying the physiological function of thionins in plants.

Amino Acid Sequence↗

PubMed2003

In silico pattern-based analysis of the human cytomegalovirus genome.

More than 200 open reading frames (ORFs) from the human cytomegalovirus genome have been reported as potentially coding for proteins. We have used two pattern-based in silico approaches to analyze this set of putative viral genes. With the help of an objective annotation method that is based on the Bio-Dictionary, a comprehensive collection of amino acid patterns that describes the currently known natural sequence space of proteins, we have reannotated all of the previously reported putative genes of the human cytomegalovirus. Also, with the help of MUSCA, a pattern-based multiple sequence alignment algorithm, we have reexamined the original human cytomegalovirus gene family definitions. Our analysis of the genome shows that many of the coded proteins comprise amino acid combinations that are unique to either the human cytomegalovirus or the larger group of herpesviruses. We have confirmed that a surprisingly large portion of the analyzed ORFs encode membrane proteins, and we have discovered a significant number of previously uncharacterized proteins that are predicted to be G-protein-coupled receptor homologues. The analysis also indicates that many of the encoded proteins undergo posttranslational modifications such as hydroxylation, phosphorylation, and glycosylation. ORFs encoding proteins with similar functional behavior appear in neighboring regions of the human cytomegalovirus genome. All of the results of the present study can be found and interactively explored online (http://cbcsrv.watson.ibm.com/virus/).

Algorithms↗

PubMed1999

GenTHREADER: an efficient and reliable protein fold recognition method for genomic sequences.

A new protein fold recognition method is described which is both fast and reliable. The method uses a traditional sequence alignment algorithm to generate alignments which are then evaluated by a method derived from threading techniques. As a final step, each threaded model is evaluated by a neural network in order to produce a single measure of confidence in the proposed prediction. The speed of the method, along with its sensitivity and very low false-positive rate makes it ideal for automatically predicting the structure of all the proteins in a translated bacterial genome (proteome). The method has been applied to the genome of Mycoplasma genitalium, and analysis of the results shows that as many as 46 % of the proteins derived from the predicted protein coding regions have a significant relationship to a protein of known structure. In some cases, however, only one domain of the protein can be predicted, giving a total coverage of 30 % when calculated as a fraction of the number of amino acid residues in the whole proteome.

Algorithms↗

PubMed2002

Y586F mutation in murine leukemia virus reverse transcriptase decreases fidelity of DNA synthesis in regions associated with adenine-thymine tracts.

Using in vivo fidelity assays in which bacterial beta-galactosidase or green fluorescent protein genes served as reporters of mutations, we have identified a murine leukemia virus (MLV) RNase H mutant (Y586F) that exhibited an increase in the retroviral mutation rate approximately 5-fold in a single replication cycle. DNA-sequencing analysis indicated that the Y586F mutation increased the frequency of substitution mutations 17-fold within 18 nt of adenine-thymine tracts (AAAA, TTTT, or AATT), which are known to induce DNA bending. Sequence alignments indicate that MLV Y586 is equivalent to HIV-1 Y501, a component of the recently described RNase H primer grip domain, which contacts and positions the DNA primer strand near the RNase H active site. The results suggest that wild-type reverse transcriptase (RT) facilitates a specific conformation of the template-primer duplex at the polymerase active site that is important for accuracy of DNA synthesis; when an adenine-thymine tract is within 18 nt of the polymerase active site, the Y586F mutant RT cannot facilitate this specific template-primer conformation, leading to an increase in the frequency of substitution mutations. These findings indicate that the RNase H primer grip can affect the template-primer conformation at the polymerase active site and that the MLV Y586 residue and template-primer conformation are important determinants of RT fidelity.

Amino Acid Sequence↗

PubMed2003

Weighted geometric docking: incorporating external information in the rotation-translation scan.

Weighted geometric docking is a prediction algorithm that matches weighted molecular surfaces. Each molecule is represented by a grid of complex numbers, storing information about the shape of the molecule in the real part and weight information in the imaginary part. The weights are based on experimental biochemical and biophysical data or on theoretical analyses of amino acid conservation or correlation patterns in multiple-sequence alignments of homologous proteins. Only a few surface residues on either one or both molecules are weighted. In contrast to methods that use postscan filtering based on biochemical information, our method incorporates the external data in the rotation-translation search, producing a different set of docking solutions biased toward solutions in which the up-weighted residues are at the interface. Similarly, interactions involving specified residues can be impeded. The weighted geometric algorithm was applied to five systems for which regular geometric docking of the unbound molecules gave poor results. We obtained much better ranking of the nearly correct prediction and higher statistical significance when weighted geometric docking was used. The method was successful even when the weighted portion of the surface corresponded only partially and approximately to the binding site.

Algorithms↗

PubMed2002

The crystal structure of YdcE, a 4-oxalocrotonate tautomerase homologue from Escherichia coli, confirms the structural basis for oligomer diversity.

The tautomerase superfamily consists of three major families represented by 4-oxalocrotonate tautomerase (4-OT), 5-(carboxymethyl)-2-hydroxymuconate isomerase (CHMI), and macrophage migration inhibitory factor (MIF). The members of this superfamily are structurally homologous proteins constructed from a simple beta-alpha-beta fold that share a key mechanistic feature; they use an amino-terminal proline, which has an unusually low pK(a), as the general base in a keto-enol tautomerization. Several new members of the 4-OT family have now been identified using PSI-BLAST and categorized into five subfamilies on the basis of multiple-sequence alignments and the conservation of key catalytic and structural residues. The members of subfamily 5, which includes a hypothetical protein designated YdcE from Escherichia coli, are predicted not to form hexamers. The crystal structure of YdcE has been determined to 1.35 A resolution and confirms that it is a dimer. In addition, YdcE complexed with (E)-2-fluoro-p-hydroxycinnamate, identified as a potent competitive inhibitor of this enzyme, as well as N-(2-hydroxyethyl)piperazine-N'-2-ethanesulfonic acid (HEPES) and benzoate are also presented. These latter crystal structures reveal the location of the active site and suggest a mechanism for the observed YdcE-catalyzed tautomerization reaction. The dimeric arrangement of YdcE represents a new structure in the 4-OT family and demonstrates structural diversity within the 4-OT family not previously reported.

Amino Acid Sequence↗

PubMed2002

Euclidian space and grouping of biological objects.

MOTIVATION: Biological objects tend to cluster into discrete groups. Objects within a group typically possess similar properties. It is important to have fast and efficient tools for grouping objects that result in biologically meaningful clusters. Protein sequences reflect biological diversity and offer an extraordinary variety of objects for polishing clustering strategies. Grouping of sequences should reflect their evolutionary history and their functional properties. Visualization of relationships between sequences is of no less importance. Tree-building methods are typically used for such visualization. An alternative concept to visualization is a multidimensional sequence space. In this space, proteins are defined as points and distances between the points reflect the relationships between the proteins. Such a space can also be a basis for model-based clustering strategies that typically produce results correlating better with biological properties of proteins. RESULTS: We developed an approach to classification of biological objects that combines evolutionary measures of their similarity with a model-based clustering procedure. We apply the methodology to amino acid sequences. On the first step, given a multiple sequence alignment, we estimate evolutionary distances between proteins measured in expected numbers of amino acid substitutions per site. These distances are additive and are suitable for evolutionary tree reconstruction. On the second step, we find the best fit approximation of the evolutionary distances by Euclidian distances and thus represent each protein by a point in a multidimensional space. The Euclidian space may be projected in two or three dimensions and the projections can be used to visualize relationships between proteins. On the third step, we find a non-parametric estimate of the probability density of the points and cluster the points that belong to the same local maximum of this density in a group. The number of groups is controlled by a sigma-parameter that determines the shape of the density estimate and the number of maxima in it. The grouping procedure outperforms commonly used methods such as UPGMA and single linkage clustering.

Algorithms↗

PubMed2000

Serum amyloid A protein in an echinoderm: its primary structure and expression during intestinal regeneration in the sea cucumber Holothuria glaberrima.

Serum amyloid A (SAA) proteins comprise a family of highly conserved apolipoproteins found in all mammals thus far investigated, and also in ducks and salmonid fishes. However, no invertebrate SAA homologues have been detected to date. Here we report the characterization of the first SAA homologue in a nonvertebrate deuterostome, the echinoderm Holothuria glaberrima. A 971-base-pair cDNA was obtained from a regenerating intestine cDNA library. The clone contains a 369-nucleotide open reading frame corresponding to a 122-amino-acid protein exhibiting a high degree of homology to members of the SAA superfamily. Sequence alignments of the holothuroid and vertebrate SAA proteins make evident a remarkable degree of conservation, even between phylogenetically disparate groups. Northern blots and immunohistochemistry show that SAA expression increases during regeneration of the holothuroid digestive tract as compared with normal nonregenerating tissue, and that the SAA protein is expressed by cells of the coelomic epithelium of the regenerating intestine. While SAA expression during the initial wound healing stage of regeneration is minimal, it increases during subsequent stages, peaking at day 15 of regeneration, concomitantly with lumen formation and the organization of the muscular layers of the regenerating digestive tract. Although in vertebrates SAA proteins may be part of a well-conserved anti-inflammatory mechanism, their exact biological function remains obscure. Our results suggest the possibility that SAA proteins, although structurally conserved, may possess enough functional diversity to participate in processes other than anti-inflammatory responses.

Amino Acid Sequence↗

PubMed2006

Dysbindin structural homologue CK1BP is an isoform-selective binding partner of human casein kinase-1.

Casein kinase-1 is a family of ubiquitous eukaryotic protein kinases that frequently function in tandem with the ubiquitin modification system to modulate protein turnover and trafficking. In Alzheimer's disease, these enzymes colocalize with ubiquitinated lesions, including neurofibrillary tangles and granulovacuolar degeneration bodies, suggesting they also play a role in disease pathogenesis. To identify binding partners that potentially regulate or recruit these enzymes toward disease lesions, a Sos-recruitment yeast two-hybrid screen was performed with human Ckidelta (the casein kinase-1 isoform most closely linked to granulovacuolar degeneration bodies) and a human brain cDNA library. All interacting clones contained a single open reading frame termed casein kinase-1 binding protein (CK1BP). On the basis of sequence alignments, CK1BP was a structural homologue of the acidic domain of dysbindin, a component of the dystrophin-associated protein complex and the biogenesis of lysosome-related organelles complex-1. CK1BP interacted with full-length Ckidelta, the isolated Ckidelta catalytic domain, Ckigamma2, -gamma3, and -epsilon in the yeast two-hybrid system, and bound Ckidelta and -epsilon in pulldown assays but did not interact with Ckialpha. Interaction with the Ckidelta catalytic domain led to concentration-dependent inhibition of protein kinase activity in the presence of protein substrates tau and alpha-synuclein. Although intact dysbindin did not bind any CK1 isoform, deletion of its coiled-coil domain yielded a protein fragment that behaved much like CK1BP in two-hybrid screens. These data suggest that the acidic domain of dysbindin and its paralogs in humans may function to recruit casein kinase-1 isoforms to protein complexes involved in multiple biological functions.

Amino Acid Sequence↗

PubMed2003

Molecular tagging of erucic acid trait in oilseed mustard (Brassica juncea) by QTL mapping and single nucleotide polymorphisms in FAE1 gene.

Molecular mapping and tagging of the erucic acid trait (C22:1) in Brassica juncea was done by a candidate gene approach. Two QTLs underlying the variation of seed erucic acid content were assigned to two linkage groups of a B. juncea map using a doubled haploid (DH) mapping population derived from high x low erucic acid F(1) hybrid. Two consensus primers corresponding to the full-length Fatty Acid Elongase 1 ( FAE1) gene, reported to be involved in the elongation of C18:1 to C22:1, were designed. PCR amplification and subsequent cloning and sequencing identified two FAE1 genes ( FAE1.1 and FAE1.2) in both high and low erucic acid mustard lines. Sequence alignment of corresponding FAE1 genes between high and low erucic acid mustard lines identified four substitution type single nucleotide polymorphisms (SNPs) in FAE1.1 and three in FAE1.2. Using the SNuPE method of SNP genotyping, these two genes were mapped to two independent loci that co-segregated with the two QTLs governing the erucic acid trait. Association of wild ( E1E2) and mutant ( e1e2) haplotypes of two FAE1 genes with erucic acid variation in two segregating populations revealed that the e1e1e2e2 genotype identified low erucic acid individuals (<2%) and E1E1E2E2 identified individuals with highest erucic acid content (>40%). The E1e1E2e2 heterozygote was found to be intermediate in phenotype. The applicability of these SNPs in marker-assisted manipulation of the erucic acid trait was verified by genotyping a set of contrasting germplasm of B. juncea belonging to two distinct gene pools (Indian and east European) and other oil-yielding Brassica species.

Acetyltransferases↗

PubMed2005

Small-world network approach to identify key residues in protein-protein interaction.

We show that protein complexes can be represented as small-world networks, exhibiting a relatively small number of highly central amino-acid residues occurring frequently at protein-protein interfaces. We further base our analysis on a set of different biological examples of protein-protein interactions with experimentally validated hot spots, and show that 83% of these predicted highly central residues, which are conserved in sequence alignments and nonexposed to the solvent in the protein complex, correspond to or are in direct contact with an experimentally annotated hot spot. The remaining 17% show a general tendency to be close to an annotated hot spot. On the other hand, although there is no available experimental information on their contribution to the binding free energy, detailed analysis of their properties shows that they are good candidates for being hot spots. Thus, highly central residues have a clear tendency to be located in regions that include hot spots. We also show that some of the central residues in the protein complex interfaces are central in the monomeric structures before dimerization and that possible information relating to hot spots of binding free energy could be obtained from the unbound structures.

Amino Acids↗

PubMed1998

Cloning and sequencing of an alpha-tubulin cDNA from Artemia franciscana: evidence for translational regulation of alpha-tubulin synthesis.

The brine shrimp, Artemia franciscana, exhibits a limited number of tubulin isotypes which change little during early postgastrula growth. In order to better understand the synthesis of alpha-tubulins during Artemia development, a cDNA termed alphaAT1 was cloned and sequenced. Alignment analyses revealed that the polypeptide encoded by alphaAT1 is similar to alpha-tubulins from other species. Hybridization of alphaAT1 to restriction-digested DNA on Southern blots produced a simple banding pattern, indicating that Artemia have a small number of alpha-tubulin genes. Probing of Northern blots demonstrated an abundant supply of alpha-tubulin mRNA in dormant cysts, emerging nauplii and instar I larvae. However, it was not until instar I larvae were produced that the amount of polysomal alpha-tubulin mRNA increased, suggesting that synthesis of the tubulin corresponding to alphaAT1 is translationally controlled. This work provides one of the few examples where tubulin synthesis is thought to be translationally regulated. Moreover, when considered in the light of previous analyses, the findings imply that cell differentiation in postgastrula Artemia and the diversification of microtubule function certain to accompany this process occur with little or no change in alpha-tubulin composition.

Amino Acid Sequence↗

PubMed1997

Predicted structure of the extracellular region of ligand-gated ion-channel receptors shows SH2-like and SH3-like domains forming the ligand-binding site.

Fast synaptic neurotransmission is mediated by ligand-gated ion-channel (LGIC) receptors, which include receptors for acetylcholine, serotonin, GABA, glycine, and glutamate. LGICs are pentamers with extracellular ligand-binding domains and form integral membrane ion channels that are selective for cations (acetylcholine and serotonin 5HT3 receptors) or anions (GABAA and glycine receptors and the invertebrate glutamate-binding chloride channel). They form a protein superfamily with no sequence similarity to any protein of known structure. Using a 1D-3D structure mapping approach, we have modeled the extracellular ligand-binding domain based on a significant match with the SH2 and SH3 domains of the biotin repressor structure. Refinement of the model based on knowledge of the large family of SH2 and SH3 structures, sequence alignments, and use of structure templates for loop building, allows the prediction of both monomer and pentamer models. These are consistent with medium-resolution electron microscopy structures and with experimental structure/function data from ligand-binding, antibody-binding, mutagenesis, protein-labeling and subunit-linking studies, and glycosylation sites. Also, the predicted polarity of the channel pore calculated from electrostatic potential maps of pentamer models of superfamily members is consistent with known ion selectivities. Using the glycine receptor alpha 1 subunit, which forms homopentamers, the monomeric and pentameric models define the agonist and antagonist (strychnine) binding sites to a deep crevice formed by an extended loop, which includes the invariant disulfide bridge, between the SH2 and SH3 domains. A detailed binding site for strychnine is reported that is in strong agreement with known structure/function data. A site for interaction of the extracellular ligand-binding domain with the activation of the M2 transmembrane helix is also suggested.

Amino Acid Sequence↗

PubMed2003

Functional expression of cinnamate 4-hydroxylase from Ammi majus L.

Total RNA was isolated from dark-grown cell suspension cultures of Ammi majus L. that had been induced with fungal elicitor or treated with water for control and used as template with cytochrome P450-specific primers for DD-RT-PCR amplifications. A cDNA clone was generated from the elicited transcripts and assigned to cinnamate 4-monooxygenase based on sequence alignments and functional expression in yeast cells. Comparison of the translated polypeptide with database accessions of heterologous cytochrome P450 monooxygenases revealed a high degree of similarity (99.6%) with 98.6% identity to cinnamic acid 4-hydroxylase from parsley, documenting the close evolutionary relationship within the Apiaceae family. Maximal activity of the Ammi hydroxylase in yeast microsomes was determined at 25 degrees C and in the pH range of 6.5-7.0 reaching 2.5 pkat/mg on average. An apparent K(m) of 8.9 microM was determined for cinnamate. Preincubations with psoralen or 8-methoxypsoralen added up to 100 microM in the presence or absence of NADPH hardly affected the turnover rate. A. majus cell cultures accumulate sets of O-prenylated umbelliferones and linear furanocoumarins besides lignin-like compounds upon treatment with elicitor, and cinnamic acid 4-hydroxylase catalyzes the initial reaction leading from the general into the various phenylpropanoid branch pathways. Correspondingly, the hydroxylase transcript abundance was induced in the elicited cells.

Amino Acid Sequence↗

PubMed2003

The complete nucleotide sequence, genome organization, and origin of human adenovirus type 11.

The complete DNA sequence and transcription map of human adenovirus type 11 are reported here. This is the first published sequence for a subgenera B human adenovirus and demonstrates a genome organization highly similar to those of other human adenoviruses. All of the genes from the early, intermediate, and late regions are present in the expected locations of the genome for a human adenovirus. The genome size is 34,794 bp in length and has a GC content of 48.9%. Sequence alignment with genomes of groups A (Ad12), C (Ad5), D (Ad17), E (Simian adenovirus 25), and F (Ad40) revealed homologies of 64, 54, 68, 75, and 52%, respectively. Detailed genomic analysis demonstrated that Ads 11 and 35 are highly conserved in all areas except the hexon hypervariable regions and fiber. Similarly, comparison of Ad11 with subgroup E SAV25 revealed poor homology between fibers but high homology in proteins encoded by all other areas of the genome. We propose an evolutionary model in which functional viruses can be reconstituted following fiber substitution from one serotype to another. According to this model either the Ad11 genome is a derivative of Ad35, from which the fiber was substituted with Ad7, or the Ad35 genome is the product of a fiber substitution from Ad21 into the Ad11 genome. This model also provides a possible explanation for the origin of group E Ads, which are evolutionarily derived from a group C fiber substitution into a group B genome.

Adenoviruses, Human↗

PubMed1993

Phylogenetic analysis of gag genes from 70 international HIV-1 isolates provides evidence for multiple genotypes.

OBJECTIVE: To determine the extent of genetic variation among internationally collected HIV-1 isolates, to analyse phylogenetic relationships and the geographic distribution of different variants. DESIGN: Phylogenetic comparison of 70 HIV-1 isolates collected in 15 countries on four continents. METHODS: To sequence the complete gag genome of HIV-1 isolates, build multiple sequence alignments and construct phylogenetic trees using distance matrix methods and maximum parsimony algorithms. RESULTS: Phylogenetic tree analysis identified seven distinct genotypes. The seven genotypes were evident by both distance matrix methods and maximum parsimony analysis, and were strongly supported by bootstrap resampling of the data. The intra-genotypic gag distances averaged 7%, whereas the inter-genotypic distances averaged 14%. The geographic distribution of variants was complex. Some genotypes have apparently migrated to several continents and many areas harbor a mixture of genotypes. Related variants may cluster in certain areas, particularly isolates from a single city collected over a short time. CONCLUSIONS: The genetic variation among HIV-1 isolates is more extensive than previously appreciated. At least seven distinct HIV-1 genotypes can be identified. Diversification, migration and establishment of local, temporal 'blooms' of particular variants may all occur concomitantly.

Africa↗

PubMed2004

CaspR: a web server for automated molecular replacement using homology modelling.

Molecular replacement (MR) is the method of choice for X-ray crystallography structure determination when structural homologues are available in the Protein Data Bank (PDB). Although the success rate of MR decreases sharply when the sequence similarity between template and target proteins drops below 35% identical residues, it has been found that screening for MR solutions with a large number of different homology models may still produce a suitable solution where the original template failed. Here we present the web tool CaspR, implementing such a strategy in an automated manner. On input of experimental diffraction data, of the corresponding target sequence and of one or several potential templates, CaspR executes an optimized molecular replacement procedure using a combination of well-established stand-alone software tools. The protocol of model building and screening begins with the generation of multiple structure-sequence alignments produced with T-COFFEE, followed by homology model building using MODELLER, molecular replacement with AMoRe and model refinement based on CNS. As a result, CaspR provides a progress report in the form of hierarchically organized summary sheets that describe the different stages of the computation with an increasing level of detail. For the 10 highest-scoring potential solutions, pre-refined structures are made available for download in PDB format. Results already obtained with CaspR and reported on the web server suggest that such a strategy significantly increases the fraction of protein structures which may be solved by MR. Moreover, even in situations where standard MR yields a solution, pre-refined homology models produced by CaspR significantly reduce the time-consuming refinement process. We expect this automated procedure to have a significant impact on the throughput of large-scale structural genomics projects. CaspR is freely available at http://igs-server.cnrs-mrs.fr/Caspr/.

Escherichia coli Proteins↗