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Biomedical subjects

K Sekar

Publications and source records attributed to K Sekar.

At least 19 recordsLinked to original sources
PubMed2006

3dSS: 3D structural superposition.

3dSS is a web-based interactive computing server, primarily designed to aid researchers, to superpose two or several 3D protein structures. In addition, the server can be effectively used to find the invariant and common water molecules present in the superposed homologous protein structures. The molecular visualization tool RASMOL is interfaced with the server to visualize the superposed 3D structures with the water molecules (invariant or common) in the client machine. Furthermore, an option is provided to save the superposed 3D atomic coordinates in the client machine. To perform the above, users need to enter Protein Data Bank (PDB)-id(s) or upload the atomic coordinates in PDB format. This server uses a locally maintained PDB anonymous FTP server that is being updated weekly. This program can be accessed through our Bioinformatics web server at the URL http://cluster.physics.iisc.ernet.in/3dss/ or http://10.188.1.15/3dss/.

Computer Graphics↗
PubMed2006

Suggestive evidence for the involvement of the second calcium and surface loop in interfacial binding: monoclinic and trigonal crystal structures of a quadruple mutant of phospholipase A2.

The crystal structures of the monoclinic and trigonal forms of the quadruple mutant K53,56,120,121M of recombinant bovine pancreatic phospholipase A2 (PLA2) have been solved and refined at 1.9 and 1.1 A resolution, respectively. Interestingly, the monoclinic form reveals the presence of the second calcium ion. Furthermore, the surface-loop residues are ordered and the conformation of residues 62-66 is similar to that observed in other structures containing the second calcium ion. On the other hand, in the trigonal form the surface loop is disordered and the second calcium is absent. Docking studies suggest that the second calcium and residues Lys62 and Asp66 from the surface loop could be involved in the interaction with the polar head group of the membrane phospholipid. It is hypothesized that the two structures of the quadruple mutant, monoclinic and trigonal, represent the conformations of PLA2 at the lipid interface and in solution, respectively. A docked structure with a phospholipid molecule and with a transition-state analogue bound, one at the active site coordinating to the catalytic calcium and the other at the second calcium site, but both at the i-face, is presented.

Animals↗
PubMed2006

Third calcium ion found in an inhibitor-bound phospholipase A2.

The lipolytic enzyme phospholipase A2 plays a crucial role in lipid metabolism and catalyzes hydrolysis of the fatty-acid ester bond at the sn-2 position of phospholipids. Here, the crystal structure (1.7 A resolution) of the triple mutant (K53,56,121M) of bovine pancreatic phospholipase A2 complexed with an organic molecule, p-methoxybenzoic acid (anisic acid), is reported. Residues 60-70 (the surface-loop residues) are ordered and adopt conformations which are different from those normally found in structures in which a second calcium ion is present. It is interesting to note that for the first time a third calcium ion has been identified. In addition, four Tris (2-amino-2-hydroxymethyl-1,3-propanediol) molecules were located. It is believed that one of the Tris molecules plays a role in clamping the third calcium ion and that another is involved in controlling the dynamics of the surface loop through hydrogen bonds.

Animals↗
PubMed2006

Inhaled nitric oxide in term and preterm infants.

Nitric oxide (NO) is a gas that has potent vasodilator properties. It can be administered via inhalation in situations where NO production is impaired and results in vasodilatation of the pulmonary capillaries. In term infants, the administration of inhaled NO, at a dose of 20 parts per million, may reduce the need for extracorporeal membrane oxygenation by reducing pulmonary vascular resistance and improving oxygenation. Inhaled NO is an approved therapy in term babies with severe hypoxemic respiratory failure. In premature infants, inhaled NO may increase bleeding time and decrease platelet aggregation resulting in an increased risk for intraventricular hemorrhage. Early administration of inhaled NO may also potentially decrease the risk for developing chronic lung disease in premature infants. However, since studies show conflicting results, inhaled NO should only be used in premature neonates following investigational review board approved protocols.

Administration, Inhalation↗
PubMed2005

Atomic resolution structure of the double mutant (K53,56M) of bovine pancreatic phospholipase A2.

The structure of the double mutant K53,56M has previously been refined at 1.9 A resolution using room-temperature data. The present paper reports the crystal structure of the same mutant K53,56M refined against 1.1 A data collected using synchrotron radiation. A total of 116 main-chain atoms from 29 residues and 44 side chains are modelled in alternate conformations. Most of the interfacial binding residues are found to be disordered and alternate conformations could be recognized. The second calcium ion-binding site residue Glu92 adopts two alternate conformations. The minor and major conformations of Glu92 correspond to the second calcium ion bound and unbound states.

Animals↗
PubMed2005

Structure of Mycobacterium smegmatis single-stranded DNA-binding protein and a comparative study involving homologus SSBs: biological implications of structural plasticity and variability in quaternary association.

The structure of Mycobacterium smegmatis single-stranded DNA-binding protein (SSB) has been determined using three data sets collected from related crystals. The structure is similar to that of its homologue from Mycobacterium tuberculosis, indicating that the clamp arrangement that stabilizes the dimer and the ellipsoidal shape of the tetramer are characteristic features of mycobacterial SSBs. The central OB fold is conserved in mycobacterial SSBs as well as those from Escherichia coli, Deinococcus radiodurans and human mitochondria. However, the quaternary structure exhibits considerable variability. The observed plasticity of the subunit is related to this variability. The crystal structures and modelling provide a rationale for the variability. The strand involved in the clamp mechanism, which leads to higher stability of the tetramer, appears to occur in all high-G+C Gram-positive bacteria. The higher stability is perhaps required by these organisms. The mode of DNA binding of mycobacterial SSBs is different from that of E. coli SSB partly on account of the difference in the shape of the tetramers. Another difference between the two modes is that the former contains additional ionic interactions and is more susceptible to salt concentration.

Crystallography, X-Ray↗
PubMed2005

Fragment Finder: a web-based software to identify similar three-dimensional structural motif.

FF (Fragment Finder) is a web-based interactive search engine developed to retrieve the user-desired similar 3D structural fragments from the selected subset of 25 or 90% non-homologous protein chains. The search is based on the comparison of the main chain backbone conformational angles (phi and ). Additionally, the queried motifs can be superimposed to find out how similar the structural fragments are, so that the information can be effectively used in molecular modeling. The engine has facilities to view the resultant superposed or individual 3D structure(s) on the client machine. The proposed web server is made freely accessible at the following URL: http://cluster.physics.iisc.ernet.in/ff/ or http://144.16.71.148/ff/.

Amino Acid Motifs↗
PubMed2005

Unusual sugar specificity of banana lectin from Musa paradisiaca and its probable evolutionary origin. Crystallographic and modelling studies.

The crystal structure of a complex of methyl-alpha-D-mannoside with banana lectin from Musa paradisiaca reveals two primary binding sites in the lectin, unlike in other lectins with beta-prism I fold which essentially consists of three Greek key motifs. It has been suggested that the fold evolved through successive gene duplication and fusion of an ancestral Greek key motif. In other lectins, all from dicots, the primary binding site exists on one of the three motifs in the three-fold symmetric molecule. Banana is a monocot, and the three motifs have not diverged enough to obliterate sequence similarity among them. Two Greek key motifs in it carry one primary binding site each. A common secondary binding site exists on the third Greek key. Modelling shows that both the primary sites can support 1-2, 1-3, and 1-6 linked mannosides with the second residue interacting in each case primarily with the secondary binding site. Modelling also readily leads to a bound branched mannopentose with the nonreducing ends of the two branches anchored at the two primary binding sites, providing a structural explanation for the lectin's specificity for branched alpha-mannans. A comparison of the dimeric banana lectin with other beta-prism I fold lectins, provides interesting insights into the variability in their quaternary structure.

Amino Acid Motifs↗
PubMed2005

CADB-2.0: Conformation Angles Database.

The Conformation Angles Data Base (CADB) is a comprehensive, authoritative and timely knowledge base with a powerful query engine developed to facilitate the retrieval of information related to the conformational angles (main chain and side chain) of the amino-acid residues present in non-redundant (both 25 and 90%) data sets. The updated version has improved options for determining the dependency of the conformation angles of a particular residue upon the flanking residues, doublet analysis, triplet analysis and analysis of a particular protein structure. It is worth mentioning that for all options a user-friendly and convenient Java graphical user interface (GUI) has been provided to display the output on the client machine. The database is accessible at the URL http://cluster.physics.iisc.ernet.in/cadb/ or http://144.16.71.148/cadb/.

Amino Acids↗
PubMed2005

SSEP-2.0: Secondary Structural Elements of Proteins.

The Secondary Structural Elements of Proteins (SSEP) database is an integrated and comprehensive knowledge base for accessing information related to all the secondary-structural elements present in non-redundant (25 and 90%) protein chains. The new version 2.0 of the database contains 2485 and 8595 protein chains from the 25 and 90% non-redundant data sets, respectively. The necessary web interfaces have been developed that enable users to visualize the three-dimensional structure of the secondary-structural element in the client machine using the free molecular-visualization program RASMOL. This source is updated at regular intervals and can be accessed through the bioinformatics web server at the URL http://cluster.physics.iisc.ernet.in/ssep or http://144.16.71.148/ssep/.

Artificial Intelligence↗
PubMed2005

Structural basis for the energetics of jacalin-sugar interactions: promiscuity versus specificity.

Jacalin, a tetrameric lectin, is one of the two lectins present in jackfruit (Artocarpus integrifolia) seeds. Its crystal structure revealed, for the first time, the occurrence of the beta-prism I fold in lectins. The structure led to the elucidation of the crucial role of a new N terminus generated by post-translational proteolysis for the lectin's specificity for galactose. Subsequent X-ray studies on other carbohydrate complexes showed that the extended binding site of jacalin consisted of, in addition to the primary binding site, a hydrophobic secondary site A composed of aromatic residues and a secondary site B involved mainly in water-bridges. A recent investigation involving surface plasmon resonance and the X-ray analysis of a methyl-alpha-mannose complex, had led to a suggestion of promiscuity in the lectin's sugar specificity. To explore this suggestion further, detailed isothermal titration calorimetric studies on the interaction of galactose (Gal), mannose (Man), glucose (Glc), Me-alpha-Gal, Me-alpha-Man, Me-alpha-Glc and other mono- and oligosaccharides of biological relevance and crystallographic studies on the jacalin-Me-alpha-Glc complex and a new form of the jacalin-Me-alpha-Man complex, have been carried out. The binding affinity of Me-alpha-Man is 20 times weaker than that of Me-alpha-Gal. The corresponding number is 27, when the binding affinities of Gal and Me-alpha-Gal, and those of Man and Me-alpha-Man are compared. Glucose (Glc) shows no measurable binding, while the binding affinity of Me-alpha-Glc is slightly less than that of Me-alpha-Man. The available crystal structures of jacalin-sugar complexes provide a convincing explanation for the energetics of binding in terms of interactions at the primary binding site and secondary site A. The other sugars used in calorimetric studies show no detectable binding to jacalin. These results and other available evidence suggest that jacalin is specific to O-glycans and its affinity to N-glycans is extremely weak or non-existent and therefore of limited value in processes involving biological recognition.

Adjuvants, Immunologic↗
PubMed2005

Community outreach for untreated schizophrenia in rural India: a follow-up study of symptoms, disability, family burden and costs.

BACKGROUND: In resource-poor countries, there remains an alarming treatment gap for people with schizophrenia, particularly those living in rural areas. Decentralization of mental health services, including community-based outreach programmes, represents one obvious strategy for bringing appropriate care to these communities. This study set out to assess the costs and effects of such a programme in rural Karnataka in India. METHOD: Eight rural communities were visited by an outreach team, who identified cases of drug-naive or currently untreated schizophrenia. Recruited cases were provided with appropriate psychotropic medication and psychosocial support, and after obtaining informed consent were assessed every 3 months over one and a half years on symptomatology, disability, family burden, resource use and costs. A repeated-measures analysis was carried out to test for significant change in these outcome measures over this period. RESULTS: A total of 100 cases of untreated schizophrenia were recruited, of whom 28% had never received antipsychotic medication and the remaining 72% had not been on medication for the past 6 months. Summary scores for psychotic symptoms, disability and family burden were all reduced significantly, with particular improvement observed at the first follow-up assessment. Increases in treatment and community outreach costs over the follow-up period were accompanied by reductions in the costs of informal-care sector visits and family care-giving time. CONCLUSIONS: Efforts to organize community-based care such as outreach services for people with schizophrenia living in more remote areas of resource-constrained countries can bring substantial benefits to patients and families alike.

Adult↗
PubMed2004

Atomic resolution (0.97 A) structure of the triple mutant (K53,56,121M) of bovine pancreatic phospholipase A2.

The enzyme phospholipase A2 catalyzes the hydrolysis of the sn-2 acyl chain of phospholipids, forming fatty acids and lysophospholipids. The crystal structure of a triple mutant (K53,56,121M) of bovine pancreatic phospholipase A2 in which the lysine residues at positions 53, 56 and 121 are replaced recombinantly by methionines has been determined at atomic resolution (0.97 A). The crystal is monoclinic (space group P2), with unit-cell parameters a = 36.934, b = 23.863, c = 65.931 A, beta = 101.47 degrees. The structure was solved by molecular replacement and has been refined to a final R factor of 10.6% (Rfree = 13.4%) using 63,926 unique reflections. The final protein model consists of 123 amino-acid residues, two calcium ions, one chloride ion, 243 water molecules and six 2-methyl-2,4-pentanediol molecules. The surface-loop residues 60-70 are ordered and have clear electron density.

Animals↗
PubMed2004

A redetermination of the structure of the triple mutant (K53,56,120M) of phospholipase A2 at 1.6 A resolution using sulfur-SAS at 1.54 A wavelength.

The crystal structure of the triple mutant K53,56,120M of bovine pancreatic phospholipase A(2) has been redetermined using sulfur single-wavelength anomalous scattering. The synchrotron data were collected at lambda = 1.54 A and the crystal diffracted to 1.6 A resolution. The program SOLVE was used to locate the heavy atoms and to estimate the initial phases and the resulting map was then subjected to RESOLVE. The output of 455 non-H atoms, including 12 S atoms, one calcium ion and one chloride ion, were then subjected to ARP/wARP followed by REFMAC. With the improved phases, the automatic model building successfully built more than 85% of the 123 residues, excluding the N- and C-terminal residues. The final crystallographic R factor is 17.7% (R(free) = 21.7%). The refined model consists of 954 non-H protein atoms, 165 water O atoms, three 2-methyl-2,4-pentanediol (MPD) molecules, one calcium ion and one chloride ion. The present work is yet another example that shows the utility of single-wavelength anomalous scattering data for solving a protein structure.

Animals↗
PubMed2004

BSDD: Biomolecules Segment Display Device--a web-based interactive display tool.

An interactive web-based display tool, Biomolecules Segment Display Device (BSDD), has been developed to search for and visualize a user-defined motif or fragment among the protein structures available in the Protein Data Bank (PDB). In addition, the tool works for the structures available in a selected sub-set of non-homologous protein structures (25% and 90% sequence identity). The graphics package RASMOL has been incorporated as an interface to visualize the three-dimensional structure of the user-defined motif. In addition, the software can be used to extract the atomic coordinates of the required fragment and save them to the client system. The atomic coordinates are updated every week from the RCSB-PDB server, and hence the results produced by BSDD are up to date at any given time. The software BSDD is available over the World Wide Web at http://iris.physics.iisc.ernet.in/bsdd or http://144.16.71.2/bsdd.

Amino Acid Motifs↗
PubMed2004

X-ray analysis of Mycobacterium smegmatis Dps and a comparative study involving other Dps and Dps-like molecules.

The structure of the DNA binding protein from starved cells from Mycobacterium smegmatis has been determined in three crystal forms and has been compared with those of similar proteins from other sources. The dodecameric molecule can be described as a distorted icosahedron. The interfaces among subunits are such that the dodecameric molecule appears to have been made up of stable trimers. The situation is similar in the proteins from Escherichia coli and Agrobacterium tumefaciens, which are closer to the M.smegmatis protein in sequence and structure than those from other sources, which appear to form a dimer first. Trimerisation is aided in the three proteins by the additional N-terminal stretches that they possess. The M.smegmatis protein has an additional C-terminal stretch compared to other related proteins. The stretch, known to be involved in DNA binding, is situated on the surface of the molecule. A comparison of the available structures permits a delineation of the rigid and flexible regions in the molecule. The subunit interfaces around the molecular dyads, where the ferroxidation centres are located, are relatively rigid. Regions in the vicinity of the acidic holes centred around molecular 3-fold axes, are relatively flexible. So are the DNA binding regions. The crystal structures of the protein from M.smegmatis confirm that DNA molecules can occupy spaces within the crystal without disturbing the arrangement of the protein molecules. However, contrary to earlier suggestions, the spaces do not need to be between layers of protein molecules. The cubic form provides an arrangement in which grooves, which could hold DNA molecules, criss-cross the crystal.

Amino Acid Sequence↗
PubMed2004

LySDB - Lysozyme Structural DataBase.

LySDB (Lysozyme Structural DataBase) is an integrated database containing 740 three-dimensional structures of lysozyme available in the Protein Data Bank. The database can be used to visualize the three-dimensional structure of the entire protein model or the substructures in which the user is interested (for example, insertions and deletions of amino acids) using the three-dimensional atomic coordinates. The database is provided with a search engine with several useful built-in facilities. The public domain graphics program RASMOL has been deployed for visualization. The three-dimensional structures used to create the database are updated at regular intervals and hence the users are provided with the current information available in the literature. The database LySDB is available over the World Wide Web and can be accessed at the URL http://iris.physics.iisc.ernet.in/lysdb/ or http://144.16.71.2/lysdb/.

Computational Biology↗