Ramesh, Vasudevan - The University of Manchester

个人简介

B.Sc ( Hons) M.Sc, Delhi University, Delhi, India Ph.D, The Australian National University, Canberra, Australia. (recipient of PhD scholarship awarded by the University). Post-doctoral Research Associate, Carnegie-Mellon University, Pittsburgh, U.S.A. Research Fellow (Leverhulme), University of Leicester, Leicester, U.K. Senior Research Fellow, University of Southampton, Southampton, U.K. "2012 Visiting Lecturer", Peking University, Beijing, China Scientific Editor (Nuclear Magnetic Resonance), Specialist Periodical Reports (1971-), Royal Society of Chemistry Publishing, Cambridge, U.K.

研究领域

Research Application of NMR spectroscopy and biophysical methods to characterise the structure, dynamics and interactions of nucleic acids (RNA,DNA) and their complexes with proteins and small molecules in solution state Inhibition of protein synthesis by RNA-binding antibiotics Project: NMR structure determination of peptidyl transferase inhibitor antibiotics and their interactions with conserved secondary structural RNA motifs of 23S ribosomal RNAs. As RNA molecules play fundamental role in prokaryotic translation and viral replication functions, they are recognized as potential target sites for therapeutic intervention by small molecules such as antibiotics. We have successfully designed and chemically synthesised two 35mer ribosomal RNA motifs of Hh and E. coli 23S rRNAs and demonstrated by NMR spectroscopic measurements that they adopt a stable, well folded A-RNA conformation in solution. The results of the NMR studies also provide direct experimental evidence for the specific binding of amicetin antibiotic to the RNA motifs and this is supported by the unconstrained molecular modelling of the amicetin-RNA complex. The model of amicetin-RNA complex highlights several key interactions between the two molecular components which may be functionally significant and a section of the model is shown in the Figure below. The model of the complex also shows a folded conformation for the amicetin antibiotic. This folding appears strained, but its stability is gained from a network of intra-molecular hydrogen bonds contacts and stacking interaction and may be structurally critical for RNA binding. The above results lay a strong foundation for further NMR studies to determine the 3D structure of the 35mer RNA motifs complexed to amicetin and the amicetin-resistant mutants. In a wider perspective, the proposed NMR studies will provide a deeper and critical insight into the molecular basis of antibiotic action and antibiotic resistance. IRES elements of Picornaviruses - Structure of conserved RNA motifs Project: Application of NMR spectroscopy and computational methods to determine the structure and interactions of the IRES RNA element of EMCV picornavirus RNA. The picornaviruses are a family of small icosahedral animal viruses that contain single-stranded RNA genomes (~ 8K bases). A salient feature of these viral RNAs is that initiation of protein synthesis has been shown to take place by a novel mechanism known as internal ribosomal entry sites (IRES). Within the IRES RNA elements, at the end of one predicted domain, is a hammerhead motif that contains a GNRA tetraloop (residues 547-550, Figure below). The importance of this tetra loop is demonstrated by the complete loss of IR

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Sadia Mohammed, Marie M. Phelan, Usman Rasul and Vasudevan Ramesh. NMR elucidation of the role of Mg2+ in the structure and stability of the conserved RNA motifs of the EMCV IRES element. Organic & Biomolecular Chemistry. 2014 January; 12: 1495-1509. eScholarID:220691 | DOI:DOI: 10.1039/c3ob41840e John King, Christos Shammas, Misbah Nareen, Moreno Lelli and Vasudevan Ramesh. NMR characterisation of a highly conserved secondary structural RNA motif of Halobacterium halobium 23S rRNA. Org. Biomol. Chem., DOI:10.1039/C3OB40295A. 2013; eScholarID:190012 Kwong Kit Chan and Vasudevan Ramesh. Conserved RNA motifs of EMCV IRES as potential building blocks to design RNA nanostructures. Chemical communications. 2012 October; 48: 11573-11575. eScholarID:180689 | DOI:10.1039/c2cc36034a Vasudevan Ramesh. 1 GHz NMR investigation of the binding of peptidyl transferase inhibitor antibiotics to conserved secondary structural motifs of 23S ribosomal RNAs. . 1st International Conference on Chemical and Structural Biology of Nucleic Acids and Proteins for Novel Drug Discovery (ISBNAP), Page 71. Beijing, Peoples Republic of China: Chinese Academy of Sciences: 2011: 71-71. eScholarID:151347 Narukulla R, Shuker D, Ramesh V, Xu Y. Unambiguous structural elucidation of base-modified purine nucleosides using NMR. Magnetic Resonance in Chemistry. 2008 January; 46(1): 1-8. eScholarID:1f175 | DOI:10.1002/mrc.2111 Shammas C, Donarski J, Ramesh V. NMR structure of the peptidyl transferase RNA inhibitor antibiotic amicetin. Magnetic Resonance in Chemistry. 2007 February; 45(2): 133-141. eScholarID:1f576 | DOI:10.1002/mrc.1932