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Biomedical subjects

D Bhatt

Publications and source records attributed to D Bhatt.

8 recordsLinked to original sources
PubMed2000

Chimeric aspartic proteinases and active site binding.

Two chimeric enzymes were constructed by exchanging domains between porcine pepsinogen and rhizopuspepsinogen in order to examine the contributions of the subsites present on different domains toward enzymatic specificity. Both chimeras exhibited the characteristic features of aspartic proteinases, such as auto-activation at low pH and abrogation of enzymatic activity by pepstatin. The activity of the chimera containing the N-terminal domain of rhizopuspepsinogen and the C-terminal domain of porcine pepsinogen (rhzNppC) could be observed by HPLC after prolonged incubation with the substrates. In contrast, the reciprocal chimera, ppNrhzC, containing the N-terminal domain of porcine pepsinogen and the C-terminal domain of rhizopuspepsinogen exhibited catalytic activity, measurable by a spectrophotometric assay. Kinetic data and inhibitor analyses strongly suggest that interdependency may exist between adjacent subsites contributed by different domains. Therefore, in order to develop an optimal substrate or inhibitor, the effect of adjacent residues of the ligand has to be examined along with the preferences for each subsite.

Journal Article↗
PubMed2000

Vocal signals in a tropical Avian species, the redvented bulbul Pycnonotus cafer: their characteristics and importance.

Acoustic signals play an important role in the lives of birds. Almost all avian species produce vocal signals in a variety of contexts either in the form of calls or songs or both. In the present study different types of vocal signals of the tropical avian species Pycnonotus cafer were characterized on the basis of their physical characteristics and context of production. This species used six types of vocal signals: contact signals, roosting signals, alarm signals, twittering signals, distress signals and begging signals. Two types of alarm signals are produced based on predation pressure. These signals are dissimilar in all physical characteristics except for dominant frequency. Although alarm signal type I and roosting signals are phonetically similar, they have completely different sonogram characteristics.

Animals↗
PubMed1998

Toward a universal inhibitor of retroviral proteases: comparative analysis of the interactions of LP-130 complexed with proteases from HIV-1, FIV, and EIAV.

One of the major problems encountered in antiviral therapy against AIDS is the emergence of viral variants that exhibit drug resistance. The sequences of proteases (PRs) from related retroviruses sometimes include, at structurally equivalent positions, amino acids identical to those found in drug-resistant forms of HIV-1 PR. The statine-based inhibitor LP-130 was found to be a universal, nanomolar-range inhibitor against all tested retroviral PRs. We solved the crystal structures of LP-130 in complex with retroviral PRs from HIV-1, feline immunodeficiency virus, and equine infectious anemia virus and compared the structures to determine the differences in the interactions between the inhibitor and the active-site residues of the enzymes. This comparison shows an extraordinary similarity in the binding modes of the inhibitor molecules. The only exceptions are the different conformations of naphthylalanine side chains at the P3/P3' positions, which might be responsible for the variation in the Ki values. These findings indicate that successful inhibition of different retroviral PRs by LP-130 is achieved because this compound can be accommodated without serious conformational differences, despite the variations in the type of residues forming the active-site region. Although strong, specific interactions between the ligand and the enzyme might improve the potency of the inhibitor, the absence of such interactions seems to favor the universality of the compound. Hence, the ability of potential anti-AIDS drugs to inhibit multiple retroviral PRs might indicate their likelihood of not eliciting drug resistance. These studies may also contribute to the development of a small-animal model for preclinical testing of antiviral compounds.

Antiviral Agents↗
PubMed1995

Structure of an inhibitor complex of the proteinase from feline immunodeficiency virus.

The crystal structure of a recombinant form of the proteinase encoded by the feline immunodeficiency virus (FIV PR) has been solved at 2 A resolution and refined to an R-factor of 0.148. The refined structure includes a peptidomimetic, statine-based inhibitor, LP-149, which is an even more potent inhibitor of HIV PR. Kinetic parameters were obtained for the cleavage of five substrates by FIV PR, and inhibition constants were measured for four inhibitors. The structure of FIV PR resembles other related retroviral enzymes although few inhibitors of HIV PR are capable of inhibiting FIV PR. The structure of FIV PR will enhance our knowledge of this class of enzymes, and will direct testing of new proteinase inhibitors in a feline animal model.

Amino Acid Sequence↗
PubMed1988

Role of cell membrane rupture in the pathogenesis of electrical trauma.

Heating due to current flow may not always be the primary cause of tissue damage in electrical injury. We have demonstrated that electric field strengths relevant to the clinical electrical injury problem are capable of permanently disrupting isolated skeletal muscle cells and altering the electrical properties of intact skeletal muscle in the absence of Joule heating effects. The field strengths used in these experiments are theoretically representative of fields at sites distant from the surface entry and exit points in many cases of electrical injury. These results provide further evidence that cell membrane disruption by large induced transmembrane potentials may explain the changes in the electrical properties of muscle observed in experimental electrical trauma (M. Chilbert, et al., J. Trauma 25: 209, 1985) and thus may contribute significantly to the extensive tissue destruction associated with electrical trauma.

Animals↗