107 research outputs found
Molecular basis of fosmidomycin's action on the human malaria parasite Plasmodium falciparum
The human malaria parasite Plasmodium falciparum is responsible for the deaths of more than a million people each year. Fosmidomycin has been proven to be efficient in the treatment of P. falciparum malaria by inhibiting 1-deoxy-D-xylulose 5-phosphate reductoisomerase (DXR), an enzyme of the non-mevalonate pathway, which is absent in humans. However, the structural details of DXR inhibition by fosmidomycin in P. falciparum are unknown. Here, we report the crystal structures of fosmidomycin-bound complete quaternary complexes of PfDXR. Our study revealed that (i) an intrinsic flexibility of the PfDXR molecule accounts for an induced-fit movement to accommodate the bound inhibitor in the active site and (ii) a cis arrangement of the oxygen atoms of the hydroxamate group of the bound inhibitor is essential for tight binding of the inhibitor to the active site metal. We expect the present structures to be useful guides for the design of more effective antimalarial compounds
Evaluation of effective resistances in pseudo-distance-regular resistor networks
In Refs.[1] and [2], calculation of effective resistances on distance-regular
networks was investigated, where in the first paper, the calculation was based
on the stratification of the network and Stieltjes function associated with the
network, whereas in the latter one a recursive formula for effective
resistances was given based on the Christoffel-Darboux identity. In this paper,
evaluation of effective resistances on more general networks called
pseudo-distance-regular networks [21] or QD type networks \cite{obata} is
investigated, where we use the stratification of these networks and show that
the effective resistances between a given node such as and all of the
nodes belonging to the same stratum with respect to
(, belonging to the -th stratum with respect
to the ) are the same. Then, based on the spectral techniques, an
analytical formula for effective resistances such that
(those nodes , of
the network such that the network is symmetric with respect to them) is given
in terms of the first and second orthogonal polynomials associated with the
network, where is the pseudo-inverse of the Laplacian of the network.
From the fact that in distance-regular networks,
is satisfied for all nodes
of the network, the effective resistances
for ( is diameter of the network which
is the same as the number of strata) are calculated directly, by using the
given formula.Comment: 30 pages, 7 figure
Diffusion-limited aggregation: A relationship between surface thermodynamics and crystal morphology
We have combined the original diffusion-limited aggregation model introduced
by Witten and Sander with the surface thermodynamics of the growing solid
aggregate. The theory is based on the consideration of the surface chemical
potential as a thermodynamic function of the temperature and nearest-neighbor
configuration. The Monte Carlo simulations on a two-dimensional square lattice
produce the broad range of shapes such as fractal dendritic structures, densely
branching patterns, and compact aggregates. The morphology diagram illustrating
the relationship between the model parameters and cluster geometry is presented
and discussed.Comment: 5 pages, 6 figure
Understanding Marine Mussel Adhesion
In addition to identifying the proteins that have a role in underwater adhesion by marine mussels, research efforts have focused on identifying the genes responsible for the adhesive proteins, environmental factors that may influence protein production, and strategies for producing natural adhesives similar to the native mussel adhesive proteins. The production-scale availability of recombinant mussel adhesive proteins will enable researchers to formulate adhesives that are water-impervious and ecologically safe and can bind materials ranging from glass, plastics, metals, and wood to materials, such as bone or teeth, biological organisms, and other chemicals or molecules. Unfortunately, as of yet scientists have been unable to duplicate the processes that marine mussels use to create adhesive structures. This study provides a background on adhesive proteins identified in the blue mussel, Mytilus edulis, and introduces our research interests and discusses the future for continued research related to mussel adhesion
- …