Single-stranded DNA is formed at various stages of DNA metabolism. It is protected from degradation by single-stranded DNA-binding proteins (SSBs). Structural variability has been observed in the quaternary arrangement of tetrameric SSBs from mycobacteria and other sources. Here we describe two novel crystal forms which illustrate the extent of structural variability. Docking studies carried out with inhibitors identified from DNA-binding assays allowed the characterization of eight distinct potential binding regions or grooves on each tetramer that circumvent structurally variable regions. Compounds known to inhibit certain bacterial SSBs were tested against Mycobacterium tuberculosis SSB (MtSSB) using DNA-binding and cellular assays. We report two compounds that inhibit MtSSB and growth of the bacterium. Together, this structural analysis reveals a strategy to exploit the variability of MtSSB for the design of inhibitors to this protein. The variability in structure of MtSSB could contribute to its susceptibility to inhibition.

Science and the associated technology have come to the centre stage of national discourse on account of Covid. The time is now appropriate for an appraisal of the structure of Indian science. We need a support system which is an elaboration of the support provided by Lakshmanaswami Mudaliar to G. N. Ramachandran who has been arguably the greatest scientist of Indian origin to have worked in the post-independence era.

Mannose-binding lectins can specifically recognize and bind complex glycan structures on pathogens and have potential as antiviral and antibacterial agents. We previously reported the structure of a lectin from an archaeal species, Mevo lectin, which has specificity toward terminal alpha 1,2 linked manno-oligosaccharides. Mycobacterium tuberculosis expresses mannosylated structures including lipoarabinomannan (ManLAM) on its surface and exploits C-type lectins to gain entry into the host cells. ManLAM structure has mannose capping with terminal alpha Man(1,2)alpha Man residues and is important for recognition by innate immune cells. Here, we aim to address the specificity of Mevo lectin toward high-mannose type glycans with terminal alpha Man(1,2)alpha Man residues and its effect on M. tuberculosis internalization by macrophages. Isothermal titration calorimetry studies demonstrated that Mevo lectin shows preferential binding toward manno-oligosaccharides with terminal alpha Man(1,2)alpha Man structures and showed a strong affinity for ManLAM, whereas it binds weakly to Mycobacterium smegmatis lipoarabinomannan, which displays relatively fewer and shorter mannosyl caps. Crystal structure of Mevo lectin complexed with a Man7D1 revealed the multivalent cross-linking interaction, which explains avidity-based high-affinity for these ligands when compared to previously studied manno-oligosaccharides lacking the specific termini. Functional studies suggest that M. tuberculosis internalization by the macrophage was impaired by binding of Mevo lectin to ManLAM present on the surface of M. tuberculosis. Selectivity shown by Mevo lectin toward glycans with terminal alpha Man(1,2)alpha Man structures, and its ability to compromise the internalization of M. tuberculosis in vitro, underscore the potential utility of Mevo lectin as a research tool to study host-pathogen interactions.

Ionospheric disturbance (ID) detected using GPS based Total Electron Content (TEC) measurements are widely used to study the morphology and dynamics of the ionosphere, and its impact on radio communication and satellite based navigation. The IDs normally derived as rate of change of TEC (ROT) between consecutive ionospheric pierce points at uniform time interval implicitly results in non-uniform spatial sampling along the GPS satellite tracks. The non-uniform spatial sampling introduces aliasing in ROT. These aliasing corrupt amplitude and Signal-to-Noise Ratio (SNR) of the detected IDs. In this study, we propose a Spatio-Periodic Leveling Algorithm (SPLA) to remove such aliasing. Efficiency of the proposed algorithm was tested by simulating the IDs along a satellite track and validated with GPS observations carried out during 2015 St. Patrick's day geomagnetic storm. Spatiotemporal, and SNR analyses of simulated and observed IDs reveal that the SPLA is (i) efficient in removing the aliases, (ii) increases the SNR on an average of 99.5% compared to ROT, (iii) removes the need of applying elevation cut-off, and (iv) expands the area of coverage up to 65%.

Crystallographic and solution studies of Mevo lectin and its complexes, the first effort of its kind on an archeal lectin, reveal a structure similar to β-prism I fold lectins from plant and animal sources, but with a quaternary association involving a ring structure with seven-fold symmetry. Each subunit in the heptamer carries one sugar binding site on the first Greek key motif. The oligomeric interface is primarily made up of a parallel β-sheet involving a strand of Greek key Ι of one subunit and Greek key ΙΙΙ from a neighbouring subunit. The crystal structures of the complexes of the lectin with mannose, αMan(1,2)αMan, αMan(1,3)αMan, a mannotriose and a mannopentose revealed a primary binding site similar to that found in other mannose specific β-prism I fold lectins. The complex with αMan(1,3)αMan provides an interesting case in which a few subunits have the reducing end at the primary binding site, while the majority have the non-reducing end at the primary binding site. The structures of complexes involving the trisaccharide and the pentasaccharide exhibit cross-linking among heptameric molecules. The observed arrangements maybe relevant to the multivalency of the lectin. Phylogenetic analysis of amino acid sequences indicates that Mevo lectin is closer to β-prism I fold animal lectins than with those of plant origin. The results presented here reinforce the conclusion regarding the existence of lectins in all three domains of life. It would also appear that lectins evolved to the present form before the three domains diverged.

Mycobacterium smegmatisMutT1 (MsMutT1) is a sanitation enzyme made up of an N-terminal Nudix hydrolase domain and a C-terminal domain resembling a histidine phosphatase. It has been established that the action of MutT1 on 8-oxo-dGTP, 8-oxo-GTP and diadenosine polyphosphates is modulated by intermolecular interactions. In order to further explore this and to elucidate the structural basis of its differential action on 8-oxo-NTPs and unsubstituted NTPs, the crystal structures of complexes ofMsMutT1 with 8-oxo-dGTP, GMPPNP and GMPPCP have been determined. Replacement soaking was used in order to ensure that the complexes were isomorphous to one another. Analysis of the structural data led to the elucidation of a relationship between the arrangements of molecules observed in the crystals, molecular plasticity and the action of the enzyme on nucleotides. The dominant mode of arrangement involving a head-to-tail sequence predominantly leads to the generation of NDPs. The other mode of packing arrangement appears to preferentially generate NMPs. This work also provides interesting insights into the dependence of enzyme action on the conformation of the ligand. The possibility of modulating the enzyme action through differences in intermolecular interactions and ligand conformations makesMsMutT1 a versatile enzyme.

Argininosuccinate lyase catalyses the reversible breakdown of argininosuccinate into arginine and fumarate and is known to form tetramers in its quaternary association. The absence of structures involving competent enzymes bound to substrate/products came in the way of the precise elucidation of the catalytic mechanism of this family of proteins. Crystal structures of the enzyme from Mycobacterium tuberculosis in an unliganded form and its complex with the substrate/products have now been determined at 2.2 and 2.7 Å, respectively. The refinement of the structure of the complex was bedevilled by the presence of a lattice translocation defect. The two tetramers in the apo‐crystals and the one in the crystals of the liganded protein, have the same structure except for the movements associated with enzyme action. Each molecule consists of an N‐domain, an M‐domain, and a C‐domain. The molecule consists of four binding sites, each made up of peptide stretches from three subunits. Three binding sites appear to be occupied by the ligand in the transition state, while the products occupy the fourth site. The structure exhibits the movement of a loop in the M‐domain and parts of the C‐domain. This is the first instance when the appropriate movements are observed in a complex with bound substrate/product. The detailed picture of the binding site, active site residues and the movements associated with catalysis thus obtained, enabled a revisit of the mechanism of action of the enzyme. © 2019 IUBMB Life, 71(5):643–652, 2019

Position time series from permanent Global Navigation Satellite System (GNSS) stations are commonly used for estimating secular velocities of discrete points on the Earth’s surface. An understanding of background noise in the GNSS position time series is essential to obtain realistic estimates of velocity uncertainties. The current study focuses on the investigation of background noise in position time series obtained from thirteen permanent GNSS stations located in Nepal Himalaya using the spectral analysis method. The power spectrum of the GNSS position time series has been estimated using the Lomb–Scargle method. The iterative nonlinear Levenberg–Marquardt (LM) algorithm has been applied to estimate the spectral index of the power spectrum. The power spectrum can be described by white noise in the high frequency zone and power law noise in the lower frequency zone. The mean and the standard deviation of the estimated spectral indices are −1.46±0.14,−1.39±0.16 and −1.53± 0.07 for north, east and vertical components, respectively. On average, the power law noise extends up to a period of ca. 21 days. For a shorter period, i.e. less than ca. 21 days, the spectra are white. The spectral index corresponding to random walk noise (ca. –2) is obtained for a site located above the base of a seismogenic zone which can be due to the combined effect of tectonic and nontectonic factors rather than a spurious monumental motion. Overall, the usefulness of investigating the background noise in the GNSS position time series is discussed.

Books reviewed in Current Science are usually authored or edited by scientists. The book presently under review is written by Rajan Gurukkal, an eminent historian, thinker and educationist. The book is, however, rich in scientific content. Gurukkal is no stranger to the Indian scientific community. He has been involved with the Indian Journal of History of Science published by the Indian National Science Academy. Furthermore, he has been a Visiting Professor at the Centre for Contemporary Studies at the Indian Institute of Science, in between his assignments as Vice-Chancellor of Mahatma Gandhi University, Kottayam and the Chairman of the Kerala Higher Education Council. Much of the book was written when Gurukkal was working in the Indian Institute of Science. Central to the narrative in the book is the history of production of scientific knowledge. Of course, the book contains much else. The book has been written with intimidating thoroughness and contains material well beyond my immediate area of competence. Therefore, it was with some trepidation that I undertook the review of the book. However, I strongly felt that this splendid book should be brought to the attention of the Indian scientific community. That is the main motivation for the present attempt.