Microbial metabolism


Several structural genomics groups from NIH sponsored Protein Structure Initiative (PSI), including the Joint Center for Structural Genomics (JCSG) from UCSD and Burnham Institute for Medical Research has compiled a large protein structure dataset, which was constructed very carefully and selectively; that is, the dataset contains only experimentally determined structures of proteins from one specific organism, the hyperthermophilic bacterium Thermotoga maritima, and those of close homologs from mesophilic bacteria. In contrast to the conclusions of previous studies, the analyses show that oligomerization order, hydrogen bonds, and secondary structure play minor roles in adaptation to hyperthermophily in bacteria. On the other hand, the data exhibit very significant increases in the density of salt-bridges and in compactness for proteins from T. maritima. The latter effect can be measured by contact order or solvent accessibility, and network analysis shows a specific increase in highly connected residues in this thermophile. These features account for changes in 96% of the protein pairs studied. The results provide a clear picture of protein thermostability in one species, and a framework for future studies of thermal adaptation.

Adam Godzik’s lab at the Burnaham Institute of Medical Research is currently constructing a “big picture” of metabolic processes in Thermatoga and in othe bacterial genomes and assimilating protein architectural information flowing from Structural Genomics (SG) efforts. protein architectural information flowing from SG has not been assimilated into mainstream research as rapidly and as widely as that generated by traditional structural biology. We believe the reason for this unanticipated situation is that, unlike traditional structural biology, structure determination at SG centers is inevitably not always – nor even routinely – accompanied by a local stream of connected, synergistic biochemical and biological research. Consequently, the vast majority of protein structures determined by SG centers lack these complementary details and are not described in high impact, peer-reviewed manuscripts, the principal way by which scientists communicate. Instead, the end result of the work of a SG center is usually a set of coordinates deposited in the PDB, information that is not readily assimilated by a typical biologist and opportunities are likely often missed since the scientific application is not recognized. As a result, data from structural genomics is only very slowly absorbed into the wider research stream, largely as correlated experimental data arises.

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