Designing a Biosensor Using a Photonic Quasi-Crystal Fiber with Fan-shaped Analyte Channel

Postprin

Generation of Few-Cycle Laser Pulses Using A Photonic Quasi-crystal Fiber

KSN wishes to thank CSIR [No: 03(1264)/12/EMR-11] for the financial support through the project.Postprin

Substrate specificity determinants of class III nucleotidyl cyclases

The two second messengers in signalling, cyclic AMP and cyclic GMP, are produced by adenylyl and guanylyl cyclases respectively. Recognition and discrimination of the substrates ATP and GTP by the nucleotidyl cyclases are vital in these reactions. Various apo-, substrate- or inhibitor-bound forms of adenylyl cyclase (AC) structures from transmembrane and soluble ACs have revealed the catalytic mechanism of ATP cyclization reaction. Previously reported structures of guanylyl cyclases represent ligand-free forms and inactive open states of the enzymes and thus do not provide information regarding the exact mode of substrate binding. The structures we present here of the cyclase homology domain of a class III AC from Mycobacterium avium (Ma1120) and its mutant in complex with ATP and GTP in the presence of calcium ion, provide the structural basis for substrate selection by the nucleotidyl cyclases at the atomic level. Precise nature of the enzyme-substrate interactions, novel modes of substrate binding and the ability of the binding pocket to accommodate diverse conformations of the substrates have been revealed by the present crystallographic analysis. This is the first report to provide structures of both the nucleotide substrates bound to a nucleotidyl cyclase. Database Coordinates and structure factors have been deposited in the Protein Data Bank with accession numbers: 5D15 (Ma1120(CHD)+ATP.Ca2+), 5D0E (Ma1120(CHD)+GTP.Ca2+), 5D0H (Ma1120(CHD)(KDA -> EGY)+ATP.Ca2+), 5D0G (Ma1120(CHD)(KDA -> EGY)+GTP.Ca2+). Enzymes Adenylyl cyclase (EC number: 4.6.1.1)

Autoinhibitory mechanism and activity-related structural changes in a mycobacterial adenylyl cyclase

An adenylyl cyclase from Mycobacterium avium, Mal 120, is a functional orthologue of a pseudogene Rv1120c from Mycobacterium tuberculosis. We report the crystal structure of Mal 120 in a monomeric form and its truncated construct as a dimer. Mal 120 exists as a monomer in solution and crystallized as a monomer in the absence of substrate or inhibitor. An additional alpha-helix present at the N-terminus of the monomeric structure blocks the active site by interacting with the substrate binding residues and occupying the dimer interface region. However, the enzyme has been found to be active in solution, indicating the movement of the helix away from the interface to facilitate the formation of active dimers in conditions favourable for catalysis. Thus, the N-terminal helix of Ma1120 keeps the enzyme in an autoinhibited state when it is not active. Deletion of this helix enabled us to crystallize the molecule as an active homodimer in the presence of a P-site inhibitor 2',5'-dideoxy-3'-ATP, or pyrophosphate along with metal ions. The substrate specifying lysine residue plays a dual role of interacting with the substrate and stabilizing the dimer. The dimerization loop region harbouring the second substrate specifying residue, an aspartate, shows significant differences in conformation and position between the monomeric and dimeric structures. Thus, this study has not only revealed that significant structural transitions are required for the interconversion of the inactive and the active forms of the enzyme, but also provided precise nature of these transitions. (C) 2015 Elsevier Inc. All rights reserved

Strategic R&D Programme on Technologies for Future Experiments - Annual Report 2021

This report summarises the activities and main achievements of the CERN strategic R&D programme on technologies for future experiments during the year 2021

Annual Report 2022

This report summarises the activities and main achievements of the CERN strategic R&D programme on technologies for future experiments during the year 202