M. A. Viswamitra

A hypothesis on a specific sequence-dependent conformation of DNA and its relation to the binding of the lac-repressor protein

The structure and properties of the double-helical form of the alternating copolymer poly(dA-dT) are considered. Different lines of evidence are interpreted in terms of a structure in which every second phosphate-diester linkage has a conformation different from that of the normal B form. A rationale for this “alternating-B” structure is given which provides an explanation for the effects of chemical modifications of the T residues on the binding of the poly(dA-dT)· poly(dA-dT) to the lac repressor of Escherichia coli.

Crystalline A-DNA: the X-ray analysis of the fragment d(G-G-T-A-T-A-C-C)

An A-DNA type double helical conformation was observed in the single crystal X-ray structure of the octamer d(G-G-T-A-T-A-C-C), 1, and its 5-bromouracil-containing analogue, 2. The structure of the isomorphous crystals (space group P 61 was solved by a search technique based on packing criteria and R-factor calculations, with use of only low order data. At the present stage of refinement the R factors are 31% for 1 and 28% for 2 at a resolution of 2.25 Å (0.225 nm). The molecules interact through their minor grooves by hydrogen bonding and base to sugar van der Waals contacts. The stable A conformation observed in the crystal may have some structural relevance to promoter regions where the T-A-T-A sequence is frequently found.

Thermostable xylanase from Thermoascus aurantiacus at ultrahigh resolution (0.89 A) at 100 K and atomic resolution (1.11 A) at 293 K refined anisotropically to small-molecule accuracy.

Thermoascus aurantiacus xylanase is a thermostable enzyme which hydrolyses xylan, a major hemicellulose component of the biosphere. The crystal structure of this F/10 family xylanase, which has a triosephosphate isomerase (TIM) barrel (beta/alpha)(8) fold, has been solved to small-molecule accuracy at atomic resolution (1.11 A) at 293 K (RTUX) and at ultrahigh resolution (0.89 A) at 100 K (CTUX) using X-ray diffraction data sets collected on a synchrotron light source, resulting in R/R(free) values of 9.94/12.36 and 9.00/10.61% (for all data), respectively. Both structures were refined with anisotropic atomic displacement parameters. The 0.89 A structure, with 177 476 observed unique reflections, was refined without any stereochemical restraints during the final stages. The salt bridge between Arg124 and Glu232, which is bidentate in RTUX, is water-mediated in CTUX, suggesting the possibility of plasticity of ion pairs in proteins, with water molecules mediating some of the alternate arrangements. Two buried waters present inside the barrel form hydrogen-bond interactions with residues in strands beta2, beta3, beta4 and beta7 and presumably contribute to structural stability. The availability of accurate structural information at two different temperatures enabled the study of the temperature-dependent deformations of the TIM-barrel fold of the xylanase. Analysis of the deviation of corresponding C(alpha) atoms between RTUX and CTUX suggests that the interior beta-strands are less susceptible to changes as a function of temperature than are the alpha-helices, which are on the outside of the barrel. betaalpha-loops, which are longer and contribute residues to the active-site region, are more flexible than alphabeta-loops. The 0.89 A structure represents one of the highest resolution structures of a protein of such size with one monomer molecule in the asymmetric unit and also represents the highest resolution TIM-barrel fold structure to date. It may provide a useful template for theoretical modelling studies of the structure and dynamics of the ubiquitous TIM-barrel fold.

Alkaloid synthesis: stereoselective approach towards fawcettimine-serratinine group of lycopodium alkaloids

The concept of carbocycle-heterocycle equivalency has been utilised to assemble the framework of fawcettimine-serratinine group of alkaloids from 1,5-cyclooctadiene through a common tricarbocyclic intermediate 3.

From cages to wedges and clefts: Design of some novel hosts based on cis, syn, cis-triquinane framework

Abstract Annulation of aromatic rings on the folded cis , syn , cis -triquinane backbone has led to the design of potential host systems 4 and 6 whose crystal structures have been determined.

Crystallization and preliminary investigations on a telomeric repeat sequence C4A2C4A2

Repeat units based on the telomeric sequence of the ciliated protozoan Tetrahymena, d(C(4)A(2))(2), have been crystallized. Cytosine-rich DNA stretches are known to reside in telomeres and centromeres of eukaryotic chromosomes, playing crucial roles in the structural stability of the chromosome in addition to their connection with cancer and aging. Preliminary investigations on the telomeric repeat sequence C(4)A(2)C(4)A(2) from CD studies and X-ray crystal data suggest it to be a right-handed interdigitated tetraplex structure with hemiprotonated C.C(+) base pairs. The molecules appear to be packed one on top of another forming a discontinuous helix along c simulating a poly-C fibre, an arrangement which maximizes the number of cytosines stacked.

New triquinane-based host molecules: binding with diamines

Synthesis of several shape-specific hosts through heteroaromatic annulation on cis,syn,cis-triquinanedione 1 and X-ray crystal structure determination of one of them, 4a, is reported. Preliminary results of complexation between cleft 5a and diamines are reported.

From cages to wedges and clefts

Abstract Annulation of aromatic rings on the folded cis , syn , cis -triquinane backbone has led to the design of potential host systems 4 and 6 whose crystal structures have been determined.