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Varatharajan Sabareesh

Bio: Varatharajan Sabareesh is an academic researcher from VIT University. The author has contributed to research in topics: Electrospray ionization & Mass spectrometry. The author has an hindex of 11, co-authored 26 publications receiving 385 citations. Previous affiliations of Varatharajan Sabareesh include Institute of Genomics and Integrative Biology & Jawaharlal Nehru Centre for Advanced Scientific Research.

Papers
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Journal ArticleDOI
23 Jan 2014-PLOS ONE
TL;DR: The results suggest that the cellular concentration of c-di-AMP can be regulated by ATP concentration as well as the hydrolysis by MtbPDE, which is novel compared to c- Di-AMP specific phosphodiesterase, YybT (or GdpP) in being a soluble protein and hydrolyzing c-Di-AMP to 5′-AMP.
Abstract: Cyclic di-AMP is a recently discovered signaling molecule which regulates various aspects of bacterial physiology and virulence. Here we report the characterization of c-di-AMP synthesizing and hydrolyzing proteins from Mycobacterium tuberculosis. Recombinant Rv3586 (MtbDisA) can synthesize c-di-AMP from ATP through the diadenylate cyclase activity. Detailed biochemical characterization of the protein revealed that the diadenylate cyclase (DAC) activity is allosterically regulated by ATP. We have identified the intermediates of the DAC reaction and propose a two-step synthesis of c-di-AMP from ATP/ADP. MtbDisA also possesses ATPase activity which is suppressed in the presence of the DAC activity. Investigations by liquid chromatography -electrospray ionization mass spectrometry have detected multimeric forms of c-di-AMP which have implications for the regulation of c-di-AMP cellular concentration and various pathways regulated by the dinucleotide. We have identified Rv2837c (MtbPDE) to have c-di-AMP specific phosphodiesterase activity. It hydrolyzes c-di-AMP to 5'-AMP in two steps. First, it linearizes c-di-AMP into pApA which is further hydrolyzed to 5'-AMP. MtbPDE is novel compared to c-di-AMP specific phosphodiesterase, YybT (or GdpP) in being a soluble protein and hydrolyzing c-di-AMP to 5'-AMP. Our results suggest that the cellular concentration of c-di-AMP can be regulated by ATP concentration as well as the hydrolysis by MtbPDE.

56 citations

Journal ArticleDOI
TL;DR: Ten new cyclic hexadepsipeptides, six isariins and four isaridins, from the fungus Isaria have been identified and characterized by high-performance liquid chromatography, coupled to tandem electrospray ionization mass spectrometry (LC-ESIMS/MS).
Abstract: Ten new cyclic hexadepsipeptides, six isariins and four isaridins, from the fungus Isaria have been identified and characterized by high-performance liquid chromatography, coupled to tandem electrospray ionization mass spectrometry (LC-ESIMS/MS). The isariins possess a β-hydroxy acid residue and five α-amino acids, while isaridins contain a β-amino acid, an α-hydroxy acid, and four α-amino acids. One- and two-dimensional NMR spectroscopy confirmed the chemical identity of some of the isariin fractions. Mass spectral fragmentation patterns of [M + H]+ ions reveal clear diagnostic fragment ions for the isariins and isaridins. Previously described cyclic depsipeptides, isarfelins from Isaria felina (Guo, Y. X.; Liu, Q. H.; Ng, T. B.; Wang H. X. Peptides 2005, 26, 2384), are now reassigned as members of the isaridin family. Examination of isaridin sequences revealed significant similarities with cyclic hexadepsipeptides such as destruxins and roseotoxins. The structure of an isariin (isariin A) investigated b...

50 citations

Journal ArticleDOI
01 Nov 2006-Peptides
TL;DR: The results establish that subtle sequence effects, which accompany post-translational modifications in Conus peptides, can have dramatic effects on target ion channels.

42 citations

Journal ArticleDOI
TL;DR: De novo mass spectrometric sequencing of two Conus peptides from the vermivorous cone snail Conus virgo reveals that the peptides belong to the class of T-superfamily conotoxins, in particular the T-1 superfamily.

39 citations

Journal ArticleDOI
TL;DR: The combined use of protonated and sodium ion adducts should prove useful in de novo sequencing of peptides, particularly of naturally occurring neutral peptides with modified N- and C-termini, for example, peptaibols.
Abstract: The fragmentations of $[M+H]^+$ and $[M+Na]^+$ adducts of neutral peptides with blocked N- and C-termini have been investigated using electrospray ion trap mass spectrometry. The N-termini of these synthetically designed peptides are blocked with a tertiarybutyloxycarbonyl (Boc) group, and the C-termini are esterified. These peptides do not possess side chains that are capable of complexation and hence the backbone amide units are the sole sites of protonation and metallation. The cleavage patterns of the protonated peptides are strikingly different from those of sodium ion adducts. While the loss of the N-terminal blocking group occurs quite readily in the case of MS/MS of $[M+Na]^+$, the cleavage of the C-terminal methoxy group seems to be a facile process in the case of MS/MS of $[M+H]^+$. Fragmentation of the protonated adducts yields only $b_n$ ions, while $y_n$ and $a_n$ ions are predominantly formed from the fragmentation of sodium ion adducts. The $a_n$ ions arising from the fragmentation of $[M+Na]^+$ lack the N terminal Boc group (and are here termed $a_n$ * ions). MS/MS of $[M+Na]^+$ species also yields $b_n$ ions of substantially lower intensities that lack the N-terminal Boc group ($b_n$*). A similar distinction between the fragmentation patterns of proton and sodium ion adducts is observed in the case of peptides possessing an N-terminal acetyl group. An example of the fragmentation of the $H^+$ and $Na^+$ adducts of a naturally occurring peptaibol from a Trichoderma species confirms that fragmentation of these two ionized species yields complementary information, useful in sequencing natural peptides. Inspection of the isotopic pattern of $b_n$ ions derived from $[M+H]^+$ adducts of peptaibols provided insights into the sequences of microheterogeneous samples. This study reveals that the combined use of protonated and sodium ion adducts should prove useful in de novo sequencing of peptides, particularly of naturally occurring neutral peptides with modified N- and C-termini, for example, peptaibols.

38 citations


Cited by
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Journal ArticleDOI
TL;DR: This review covers the literature published in 2014 for marine natural products, with 1116 citations referring to compounds isolated from marine microorganisms and phytoplankton, green, brown and red algae, sponges, cnidarians, bryozoans, molluscs, tunicates, echinoderms, mangroves and other intertidal plants and microorganisms.

4,649 citations

Journal ArticleDOI
TL;DR: Recent advances in antimalarial drug discovery from natural sources are presented, including plant extracts, and compounds isolated from plants, bacteria, fungi and marine organisms, which offer new and novel scaffolds for development as antimalarials.

400 citations

Journal ArticleDOI
TL;DR: Conformational Variability and Biological Activity 677 8.1.
Abstract: 6. ω Amino Acids in Hairpins 672 6.1. Insertion into Turn Segments 672 6.2. Extended Strands 673 7. Conformational Representations 673 7.1. Conformationally Constrained Residues 675 8. Conformational Variability and Biological Activity 677 8.1. Conformational Variability in Solution 677 8.2. Biological Activity of Synthetic Peptides 678 9. Revisiting Hydrogen-Bonded Rings and Polypeptide Helices 678

269 citations

Journal ArticleDOI
13 Sep 2012-PLOS ONE
TL;DR: The fragmentation module of a freely available open-source software, mMass, is extended to allow for cyclic peptide tandem mass spectra annotation and interpretation to be superior to other currently available tools concerning both usability and annotation extensiveness.
Abstract: Natural or synthetic cyclic peptides often possess pronounced bioactivity. Their mass spectrometric characterization is difficult due to the predominant occurrence of non-proteinogenic monomers and the complex fragmentation patterns observed. Even though several software tools for cyclic peptide tandem mass spectra annotation have been published, these tools are still unable to annotate a majority of the signals observed in experimentally obtained mass spectra. They are thus not suitable for extensive mass spectrometric characterization of these compounds. This lack of advanced and user-friendly software tools has motivated us to extend the fragmentation module of a freely available open-source software, mMass (http://www.mmass.org), to allow for cyclic peptide tandem mass spectra annotation and interpretation. The resulting software has been tested on several cyanobacterial and other naturally occurring peptides. It has been found to be superior to other currently available tools concerning both usability and annotation extensiveness. Thus it is highly useful for accelerating the structure confirmation and elucidation of cyclic as well as linear peptides and depsipeptides.

237 citations

Journal ArticleDOI
TL;DR: When integrated into a larger lipidomics workflow, LipidMatch may increase the probability of finding lipid-based biomarkers and determining etiology of disease by covering a greater portion of the lipidome and using annotation which does not over-report biologically relevant structural details of identified lipid molecules.
Abstract: Lipids are ubiquitous and serve numerous biological functions; thus lipids have been shown to have great potential as candidates for elucidating biomarkers and pathway perturbations associated with disease. Methods expanding coverage of the lipidome increase the likelihood of biomarker discovery and could lead to more comprehensive understanding of disease etiology. We introduce LipidMatch, an R-based tool for lipid identification for liquid chromatography tandem mass spectrometry workflows. LipidMatch currently has over 250,000 lipid species spanning 56 lipid types contained in in silico fragmentation libraries. Unique fragmentation libraries, compared to other open source software, include oxidized lipids, bile acids, sphingosines, and previously uncharacterized adducts, including ammoniated cardiolipins. LipidMatch uses rule-based identification. For each lipid type, the user can select which fragments must be observed for identification. Rule-based identification allows for correct annotation of lipids based on the fragments observed, unlike typical identification based solely on spectral similarity scores, where over-reporting structural details that are not conferred by fragmentation data is common. Another unique feature of LipidMatch is ranking lipid identifications for a given feature by the sum of fragment intensities. For each lipid candidate, the intensities of experimental fragments with exact mass matches to expected in silico fragments are summed. The lipid identifications with the greatest summed intensity using this ranking algorithm were comparable to other lipid identification software annotations, MS-DIAL and Greazy. For example, for features with identifications from all 3 software, 92% of LipidMatch identifications by fatty acyl constituents were corroborated by at least one other software in positive mode and 98% in negative ion mode. LipidMatch allows users to annotate lipids across a wide range of high resolution tandem mass spectrometry experiments, including imaging experiments, direct infusion experiments, and experiments employing liquid chromatography. LipidMatch leverages the most extensive in silico fragmentation libraries of freely available software. When integrated into a larger lipidomics workflow, LipidMatch may increase the probability of finding lipid-based biomarkers and determining etiology of disease by covering a greater portion of the lipidome and using annotation which does not over-report biologically relevant structural details of identified lipid molecules.

216 citations