Biomedical subjects
Publications and source records attributed to T J Hubbard.
An ever increasing number of protein sequences are being compared, partly because of the availability of full sets of protein sequences from several completed genome-sequencing projects. The resulting problem of scale has shifted the emphasis of sequence analysis method development from sensitivity and flexibility, which relies on manual intervention and interpretation, to the automatic generation of results of known reliability.
Structural classifications aid the interpretation of proteins by describing degrees of structural and evolutionary relatedness. They have also recently revealed strikingly skewed distributions at all levels; for example, a small number of folds are far more common than others, and just a few superfamilies are known to have diverged widely. The classifications also provide an indication of the total number of superfamilies in nature.
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The three-dimensional structure of the GroES monomer and its interaction with GroEL has been predicted using a combination of prediction tools and experimental data obtained by biophysical [electron microscope (EM), Fourier transform infrared (FTIR), and nuclear magnetic resonance (NMR)] and biochemical techniques. The GroES monomer, according to the prediction, is composed of eight beta-strands forming a beta-barrel with loose ends. In the model, beta-strands 5-8 run along the outer surface of GroES, forming an antiparallel beta-sheet with beta 4 loosely bound to one of the edges. beta-strands 1-3 would then be parallel and placed in the interior of the molecule. Loops 1-3 would face the internal cavity of the GroEL-GroES complex, and together with conserved residues in loops 5 and 7, would form the active surface interacting with GroEL.
Protein structure predictions were submitted for 9 of the target sequences in the competition that ran during 1994. Targets sequences were selected that had no known homology with any sequence of known structure and were members of a reasonably sized family of related but divergent sequences. The objective was either to recognize a compatible fold for the target sequence in the database of known structures or to predict ab initio its rough 3D topology. The main tools used were Hidden Markov models (HMM) for fold recognition, a beta-strand pair potential to predict beta-sheet topology, and the PHD server for secondary structure prediction. Compatible folds were correctly identified in a number of cases and the beta-strand pair potential was shown to be a useful tool for ab initio topology prediction.
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We present a program- and machine-independent standard for annotating macromolecular structures. Data encoded by this specification may be used for communicating information about structures and for exchanging it between different computer systems. The format consists of a set of ASN.1 objects which are mechanically straightforward to parse, but are also easy for humans to create and understand. It differs from all other related standards in that it specifies how a molecule should be displayed without requiring a custom format for the coordinate data.
Recreational rocket injuries can result in massive destruction of facial soft tissues and bone and can produce long-term sequelae. This study reviews the cases of three patients who arrived at our medical center within a 3-week period in July 1990 who sustained severe craniofacial injuries from fireworks. A timely multidisciplinary approach is important in the care of these injuries, since there are usually associated serious ophthalmologic and cranial injuries that require immediate attention. We present the management dilemmas confronting the personnel who treat such injuries as well as tips on avoiding long-term complications.
Recently some heat-shock proteins have been linked to functions of 'chaperoning' protein folding in vivo. Here current experimental evidence is reviewed and possible requirements for such an activity are discussed. It is proposed that one mode of chaperone action is to actively unfold misfolded or badly aggregated proteins to a conformation from which they could refold spontaneously; that improperly folded proteins are recognized by excessive stretches of solvent-exposed backbone, rather than by exposed hydrophobic patches; and that the molecular mechanism for unfolding is either repeated binding and dissociation ('plucking') or translocation of the protein backbone through a binding cleft ('threading'), allowing the threaded chain to refold spontaneously. The observed hydrolysis of ATP would provide the energy for active unfolding. These hypotheses can be applied to both monomeric folding and oligomeric assembly and are sufficiently detailed to be open to directed experimental verification.
The three-dimensional structures of 41 homologous proteins (belonging to eight families) were compared by pairwise superposition. A subset of 'core' residues was defined as those whose side chains have less than 7% of their surface exposed to solvent. This subset has significantly higher sequence identity and lower root mean square (RMS) alpha carbon separation than for all topologically equivalent residues in the structure, when members of a protein family are superposed. For such superpositions the relationship between RMS distance and percentage sequence identity of this subset of residues is similar to that for all equivalent residues, although some variation is observed between families of proteins which are predominantly beta sheet and those which are mainly alpha helix. The definition of a structurally more conserved core may be useful in model building proteins from an homologous family. The RMS differences of coordinates of structures of proteins with identical sequences are found to be related to the resolutions of the structures.
Four major heat-shock proteins (hsps) with apparent molecular masses of 84, 69, 32 and 22 kDa were detected in exponentially growing stationary phase and sporulating cells of Bacillus subtilis heat-shocked from 30 to 43 degrees C. The most abundant, hsp69, is probably analogous to the E. coli groEL protein. These proteins were transiently inducible by heat-shock. Partial purification of RNA polymerase revealed several other minor hsps. One of these, a 48 kDa polypeptide probably corresponds to sigma 43. The synthesis of this polypeptide and at least two other proteins appeared to be under sporulation and heat-shock regulation and was affected by the SpoOA mutation.
Hospital admissions for childhood asthma to three university affiliated hospitals in the Washington D.C. area (Children's Hospital National Medical Center, CHNMC, Prince George's General Hospital, PGGH, and Holy Cross Hospital, HCH) for the period 1961-1981 increased at least three to 18 fold. The over-all population of children less than or equal to 14 years of age increased, at most, only 1.5 fold by 1970, and thereafter decreased gradually until the end of the study. This increase in pediatric asthma hospitalizations has occurred despite significant improvements in the ambulatory management of the asthmatic child. In particular, the amount of specific anti-asthmatic medication prescribed for these patients has grown markedly. The increased hospitalization is most likely due to an increase in the occurrence of severe asthma in children, particularly black children.