Biomedical subjects

Peter M Bowers

Publications and source records attributed to Peter M Bowers.

5 recordsLinked to original sources

PubMed2006

The structure and computational analysis of Mycobacterium tuberculosis protein CitE suggest a novel enzymatic function.

Fatty acid biosynthesis is essential for the survival of Mycobacterium tuberculosis and acetyl-coenzyme A (acetyl-CoA) is an essential precursor in this pathway. We have determined the 3-D crystal structure of M. tuberculosis citrate lyase beta-subunit (CitE), which as annotated should cleave protein bound citryl-CoA to oxaloacetate and a protein-bound CoA derivative. The CitE structure has the (beta/alpha)(8) TIM barrel fold with an additional alpha-helix, and is trimeric. We have determined the ternary complex bound with oxaloacetate and magnesium, revealing some of the conserved residues involved in catalysis. While the bacterial citrate lyase is a complex with three subunits, the M. tuberculosis genome does not contain the alpha and gamma subunits of this complex, implying that M. tuberculosis CitE acts differently from other bacterial CitE proteins. The analysis of gene clusters containing the CitE protein from 168 fully sequenced organisms has led us to identify a grouping of functionally related genes preserved in M. tuberculosis, Rattus norvegicus, Homo sapiens, and Mus musculus. We propose a novel enzymatic function for M. tuberculosis CitE in fatty acid biosynthesis that is analogous to bacterial citrate lyase but producing acetyl-CoA rather than a protein-bound CoA derivative.

Amino Acid Sequence↗

PubMed2006

An exploratory study of total mercury levels in archaeological caribou hair from northwest Alaska.

Over the past ten years, total mercury (THg) levels have been surveyed in Alaskan wildlife and fish as part of the Arctic Monitoring and Assessment (AMAP). Beyond these studies there is little historical data on THg levels in important subsistence species for people in Alaska. A survey of THg in caribou hair from archaeological deposits would provide data to develop temporal trends for this region of the Arctic. Caribou hair from a Western Thule settlement beneath the Alaska native village of Deering (ca. AD 1150) show variability in hair THg values, with a mean level (86 ng/g) which is in the range that is observed in modern Rangifer sp. (caribou and reindeer). Hair from House 1 had a THg mean level of 99.6 ng/g and hair from House 2 had a THg mean of 64.2 ng/g. This is the earliest reported record of mercury in caribou associated with human subsistence activities in the western North American Arctic, and is a first step toward compilation of a needed database through which to measure and evaluate exposure to mercury by people who rely heavily on caribou as a food source. We hypothesize that similarity in mercury values in archaeological samples of caribou and in contemporary samples would give an additional perspective on human exposure to mercury through caribou harvest and consumption today. Since this hypothesis will be more useful if evaluated at a regional rather than global scale, further studies will be needed at different archaeological sites across Alaska to determine the generality of this observation in relation to geographic scale.

Alaska↗

PubMed2005

Utilizing logical relationships in genomic data to decipher cellular processes.

The wealth of available genomic data has spawned a corresponding interest in computational methods that can impart biological meaning and context to these experiments. Traditional computational methods have drawn relationships between pairs of proteins or genes based on notions of equality or similarity between their patterns of occurrence or behavior. For example, two genes displaying similar variation in expression, over a number of experiments, may be predicted to be functionally related. We have introduced a natural extension of these approaches, instead identifying logical relationships involving triplets of proteins. Triplets provide for various discrete kinds of logic relationships, leading to detailed inferences about biological associations. For instance, a protein C might be encoded within an organism if, and only if, two other proteins A and B are also both encoded within the organism, thus suggesting that gene C is functionally related to genes A and B. The method has been applied fruitfully to both phylogenetic and microarray expression data, and has been used to associate logical combinations of protein activity with disease state phenotypes, revealing previously unknown ternary relationships among proteins, and illustrating the inherent complexities that arise in biological data.

Algorithms↗

PubMed2004

Use of logic relationships to decipher protein network organization.

A major focus of genome research is to decipher the networks of molecular interactions that underlie cellular function. We describe a computational approach for identifying detailed relationships between proteins on the basis of genomic data. Logic analysis of phylogenetic profiles identifies triplets of proteins whose presence or absence obey certain logic relationships. For example, protein C may be present in a genome only if proteins A and B are both present. The method reveals many previously unidentified higher order relationships. These relationships illustrate the complexities that arise in cellular networks because of branching and alternate pathways, and they also facilitate assignment of cellular functions to uncharacterized proteins.

Bacterial Physiological Phenomena↗

PubMed2004

Prolinks: a database of protein functional linkages derived from coevolution.

The advent of whole-genome sequencing has led to methods that infer protein function and linkages. We have combined four such algorithms (phylogenetic profile, Rosetta Stone, gene neighbor and gene cluster) in a single database--Prolinks--that spans 83 organisms and includes 10 million high-confidence links. The Proteome Navigator tool allows users to browse predicted linkage networks interactively, providing accompanying annotation from public databases. The Prolinks database and the Proteome Navigator tool are available for use online at http://dip.doe-mbi.ucla.edu/pronav.

ATP Synthetase Complexes↗