Biomedical subjects

Cherian Zachariah

Publications and source records attributed to Cherian Zachariah.

5 recordsLinked to original sources

PubMed2006

An alternative bactericidal mechanism of action for lantibiotic peptides that target lipid II.

Lantibiotics are polycyclic peptides containing unusual amino acids, which have binding specificity for bacterial cells, targeting the bacterial cell wall component lipid II to form pores and thereby lyse the cells. Yet several members of these lipid II-targeted lantibiotics are too short to be able to span the lipid bilayer and cannot form pores, but somehow they maintain their antibacterial efficacy. We describe an alternative mechanism by which members of the lantibiotic family kill Gram-positive bacteria by removing lipid II from the cell division site (or septum) and thus block cell wall synthesis.

Anti-Bacterial Agents↗

PubMed2006

NMR analysis of Caenorhabditis elegans FLP-18 neuropeptides: implications for NPR-1 activation.

Phe-Met-Arg-Phe-NH2 (FMRFamide)-like peptides (FLPs) are the largest neuropeptide family in animals, particularly invertebrates. FLPs are characterized by a C-N-terminal gradient of decreasing amino acid conservation. Neuropeptide receptor 1 (NPR-1) is a G-protein coupled receptor (GPCR), which has been shown to be a strong regulator of foraging behavior and aggregation responses in Caenorhabditis elegans. Recently, ligands for NPR-1 were identified as neuropeptides coded by the precursor genes flp-18 and flp-21 in C. elegans. The flp-18 gene encodes eight FLPs including DFDGAMPGVLRF-NH2 and EMPGVLRF-NH2. These peptides exhibit considerably different activities on NPR-1, with the longer one showing a lower potency. We have used nuclear magnetic resonance and biological activity to investigate structural features that may explain these activity differences. Our data demonstrate that long-range electrostatic interactions exist between N-terminal aspartates and the C-terminal penultimate arginine as well as N-terminal hydrogen-bonding interactions that form transient loops within DFDGAMPGVLRF-NH2. We hypothesize that these loops, along with peptide charge, diminish the activity of this peptide on NPR-1 relative to that of EMPGVLRF-NH2. These results provide some insight into the large amino acid diversity in FLPs.

Amino Acid Sequence↗

PubMed2006

Comparison of the performance of round and rectangular wire in small solenoids for high-field NMR.

This paper considers the effects of conductor geometry on the performance of small solenoidal coils for high-field NMR. First, a simple analytical model is presented for investigating the effects of conductor geometry on the current distribution in such coils. The model was used to derive optimum parameters for coils constructed from wire with either rectangular or circular cross-sections as a function of the length-to-diameter ratio. Second, a commercial software package utilizing full three-dimensional finite-element solutions to Maxwell's equations was used to confirm the basic findings of the simple analytical model, and also to compare simulated S/N estimations with experimental NMR spectra acquired with 2.5 mm and 1.0 mm-diameter solenoid coils: reasonable agreement was found. Third, as a demonstration of the usefulness of such coils for mass-limited samples, multidimensional experiments were performed at 750 MHz on approximately 4.7 nmol (41 microg) of PF1061, a protein from Pyrococcus furiosus.

Equipment Design↗

PubMed2003

Structure and dynamics of the lantibiotic mutacin 1140.

Mutacin 1140 is a member of a family of ribosomally synthesized peptide bacteriocins called lantibiotics (lanthionine-containing antibiotics) and is produced by the Gram-positive bacterium Streptococcus mutans. Mutacin 1140 has been shown to be effective against a broad array of Gram-positive bacteria. Chromatography and mass spectroscopy data suggested that mutacin 1140 forms a small compact structure. Nuclear magnetic resonance (NMR) data and restrained molecular dynamics simulations showed that mutacin 1140 interconverts between multiple structures. Calculations of scalar (J) coupling constants showed the best agreement with experimental values when the entire population-weighted ensemble of structures was used, providing independent support for the ensemble. Representative structures from each major group in the ensemble had a common feature in which they are all kinked around the hinge region forming a horseshoe-like shape, and the regions of flexibility of the molecule were limited and well-defined. The structures determined in this study provide a starting point for modeling the mutacin 1140-membrane interactions and pore formation.

Amino Acid Sequence↗

PubMed2003

Fast chain contraction during protein folding: "foldability" and collapse dynamics.

Theory indicates that at least some proteins will undergo a rapid and unimpeded collapse, like a disorganized hydrophobic chain, prior to folding. Yet experiments continue to find signs of an organized, or barrier-limited, collapse in even the fastest (approximately mus) folding proteins. Does the kinetic barrier represent a signature of the equilibrium "foldability" of these molecules? We have measured the rate of chain contraction in two nonfolding analogs of a very fast-collapsing protein. We find that these chains contract on the same time scale (approximately 10(-5)s) as the natural protein, and both pass over an energetic barrier at least as large as that encountered by the protein. The equilibrium foldability of the native structure therefore does not alone determine the dynamics of collapse; even the disordered chains contract approximately 1000x slower than expected for an ideal chain.

Animals↗