Horizontal gene transfer and assortative recombination within the Acinetobacter baumannii clinical population provide genetic diversity at the single carO gene, encoding a major outer membrane protein channel.

We described previously the presence in Acinetobacter baumannii of a novel outer membrane (OM) protein, CarO, which functions as an L-ornithine OM channel and whose loss was concomitant with increased carbapenem resistance among clonally related nosocomial isolates of this opportunistic pathogen. Here, we describe the existence of extensive genetic diversity at the carO gene within the A. baumannii clinical population.

PSiFR: an integrated resource for prediction of protein structure and function.

Unlabelled: In the post-genomic era, the annotation of protein function facilitates the understanding of various biological processes. To extend the range of function annotation methods to the twilight zone of sequence identity, we have developed approaches that exploit both protein tertiary structure and/or protein sequence evolutionary relationships. To serve the scientific community, we have integrated the structure prediction tools, TASSER, TASSER-Lite and METATASSER, and the functional inference tools, FINDSITE, a structure-based algorithm for binding site prediction, Gene Ontology molecular function inference and ligand screening, EFICAz(2), a sequence-based approach to enzyme function inference and DBD-hunter, an algorithm for predicting DNA-binding proteins and associated DNA-binding residues, into a unified web resource, Protein Structure and Function prediction Resource (PSiFR).

The continuity of protein structure space is an intrinsic property of proteins.

The classical view of the space of protein structures is that it is populated by a discrete set of protein folds. For proteins up to 200 residues long, by using structural alignments and building upon ideas of the completeness and continuity of structure space, we show that nearly any structure is significantly related to any other using a transitive set of no more than 7 intermediate structurally related proteins. This result holds for all structures in the Protein Data Bank, even when structural relationships between evolutionary related proteins (as detected by threading or functional analyses) are excluded.

EFICAz2: enzyme function inference by a combined approach enhanced by machine learning.

Background: We previously developed EFICAz, an enzyme function inference approach that combines predictions from non-completely overlapping component methods. Two of the four components in the original EFICAz are based on the detection of functionally discriminating residues (FDRs). FDRs distinguish between member of an enzyme family that are homofunctional (classified under the EC number of interest) or heterofunctional (annotated with another EC number or lacking enzymatic activity).

Identification of metabolites with anticancer properties by computational metabolomics.

Background: Certain endogenous metabolites can influence the rate of cancer cell growth. For example, diacylglycerol, ceramides and sphingosine, NAD+ and arginine exert this effect by acting as signaling molecules, while carrying out other important cellular functions. Metabolites can also be involved in the control of cell proliferation by directly regulating gene expression in ways that are signaling pathway-independent, e.

The mosaic genome of Anaeromyxobacter dehalogenans strain 2CP-C suggests an aerobic common ancestor to the delta-proteobacteria.

Anaeromyxobacter dehalogenans strain 2CP-C is a versaphilic delta-Proteobacterium distributed throughout many diverse soil and sediment environments. 16S rRNA gene phylogenetic analysis groups A. dehalogenans together with the myxobacteria, which have distinguishing characteristics including strictly aerobic metabolism, sporulation, fruiting body formation, and surface motility.

Modulation of the enzymatic efficiency of ferredoxin-NADP(H) reductase by the amino acid volume around the catalytic site.

Ferredoxin (flavodoxin)-NADP(H) reductases (FNRs) are ubiquitous flavoenzymes that deliver NADPH or low-potential one-electron donors (ferredoxin, flavodoxin, adrenodoxin) to redox-based metabolic reactions in plastids, mitochondria and bacteria. Plastidic FNRs are quite efficient reductases. In contrast, FNRs from organisms possessing a heterotrophic metabolism or anoxygenic photosynthesis display turnover numbers 20- to 100-fold lower than those of their plastidic and cyanobacterial counterparts.

Aerobic uranium (VI) bioprecipitation by metal-resistant bacteria isolated from radionuclide- and metal-contaminated subsurface soils.

In this study, the immobilization of toxic uranium [U(VI)] mediated by the intrinsic phosphatase activities of naturally occurring bacteria isolated from contaminated subsurface soils was examined. The phosphatase phenotypes of strains belonging to the genera, Arthrobacter, Bacillus and Rahnella, previously isolated from subsurface soils at the US Department of Energy's (DOE) Oak Ridge Field Research Center (ORFRC), were determined. The ORFRC represents a unique, extreme environment consisting of highly acidic soils with co-occurring heavy metals, radionuclides and high nitrate concentrations.

High precision multi-genome scale reannotation of enzyme function by EFICAz.

Background: The functional annotation of most genes in newly sequenced genomes is inferred from similarity to previously characterized sequences, an annotation strategy that often leads to erroneous assignments. We have performed a reannotation of 245 genomes using an updated version of EFICAz, a highly precise method for enzyme function prediction.

Results: Based on our three-field EC number predictions, we have obtained lower-bound estimates for the average enzyme content in Archaea (29%), Bacteria (30%) and Eukarya (18%).

On the origin and highly likely completeness of single-domain protein structures.

The size and origin of the protein fold universe is of fundamental and practical importance. Analyzing randomly generated, compact sticky homopolypeptide conformations constructed in generic simplified and all-atom protein models, all have similar folds in the library of solved structures, the Protein Data Bank, and conversely, all compact, single-domain protein structures in the Protein Data Bank have structural analogues in the compact model set. Thus, both sets are highly likely complete, with the protein fold universe arising from compact conformations of hydrogen-bonded, secondary structures.

Prediction of physical protein-protein interactions.

Many essential cellular processes such as signal transduction, transport, cellular motion and most regulatory mechanisms are mediated by protein-protein interactions. In recent years, new experimental techniques have been developed to discover the protein-protein interaction networks of several organisms. However, the accuracy and coverage of these techniques have proven to be limited, and computational approaches remain essential both to assist in the design and validation of experimental studies and for the prediction of interaction partners and detailed structures of protein complexes.

TASSER: an automated method for the prediction of protein tertiary structures in CASP6.

The recently developed TASSER (Threading/ASSembly/Refinement) method is applied to predict the tertiary structures of all CASP6 targets. TASSER is a hierarchical approach that consists of template identification by the threading program PROSPECTOR_3, followed by tertiary structure assembly via rearranging continuous template fragments. Assembly occurs using parallel hyperbolic Monte Carlo sampling under the guide of an optimized, reduced force field that includes knowledge-based statistical potentials and spatial restraints extracted from threading alignments.

EFICAz: a comprehensive approach for accurate genome-scale enzyme function inference.

EFICAz (Enzyme Function Inference by Combined Approach) is an automatic engine for large-scale enzyme function inference that combines predictions from four different methods developed and optimized to achieve high prediction accuracy: (i) recognition of functionally discriminating residues (FDRs) in enzyme families obtained by a Conservation-controlled HMM Iterative procedure for Enzyme Family classification (CHIEFc), (ii) pairwise sequence comparison using a family specific Sequence Identity Threshold, (iii) recognition of FDRs in Multiple Pfam enzyme families, and (iv) recognition of multiple Prosite patterns of high specificity. For FDR (i.e.

Functional plasticity and catalytic efficiency in plant and bacterial ferredoxin-NADP(H) reductases.

Ferredoxin (flavodoxin)-NADP(H) reductases (FNRs) are ubiquitous flavoenzymes that deliver NADPH or low potential one-electron donors (ferredoxin, flavodoxin, adrenodoxin) to redox-based metabolisms in plastids, mitochondria and bacteria. Two great families of FAD-containing proteins displaying FNR activity have evolved from different and independent origins. The enzymes present in mitochondria and some bacterial genera are members of the structural superfamily of disulfide oxidoreductases whose prototype is glutathione reductase.

Large-scale assessment of the utility of low-resolution protein structures for biochemical function assignment.

Motivation: Several protein function prediction methods employ structural features captured in three-dimensional (3D) descriptors of biologically relevant sites. These methods are successful when applied to high-resolution structures, but their detection ability in lower resolution predicted structures has only been tested for a few cases.

Results: A method that automatically generates a library of 3D functional descriptors for the structure-based prediction of enzyme active sites (automated functional templates, 593 in total for 162 different enzymes), based on functional and structural information automatically extracted from public databases, has been developed and evaluated using decoy structures.

TOUCHSTONE: a unified approach to protein structure prediction.

We have applied the TOUCHSTONE structure prediction algorithm that spans the range from homology modeling to ab initio folding to all protein targets in CASP5. Using our threading algorithm PROSPECTOR that does not utilize input from metaservers, one threads against a representative set of PDB templates. If a template is significantly hit, Generalized Comparative Modeling designed to span the range from closely to distantly related proteins from the template is done.

Multimeric threading-based prediction of protein-protein interactions on a genomic scale: application to the Saccharomyces cerevisiae proteome.

MULTIPROSPECTOR, a multimeric threading algorithm for the prediction of protein-protein interactions, is applied to the genome of Saccharomyces cerevisiae. Each possible pairwise interaction among more than 6000 encoded proteins is evaluated against a dimer database of 768 complex structures by using a confidence estimate of the fold assignment and the magnitude of the statistical interfacial potentials. In total, 7321 interactions between pairs of different proteins are predicted, based on 304 complex structures.