Modern NMR spectroscopy of proteins and peptides in solution and its relevance to drug design

The knowledge of the three-dimensional (3D) structures and conformational dynamics of proteins and peptides is important for the understanding of biochemical and genetic data derived for these molecules. This understanding can ultimately be of help in drug design. We describe here the role of Nuclear Magnetic Resonance (NMR) spectroscopy in this process for three distinct situations: for small proteins, where relatively simple NMR methods can be used for full 3D structure determination; for larger proteins that require multinuclear multidimensional NMR but for which full 3D structures can still be obtained; and for small peptides that are studied in interaction with macromolecules (receptors) using specialized NMR techniques. A fourth situation, pertaining to large systems where only partial structural information can be obtained from NMR data, is briefly discussed. Molecules of interest to the biomedical field (C5a and stromelysin) are discussed as examples.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43356/1/11091_2005_Article_BF02174537.pd

Troglomorphic pseudoscorpions (Arachnida: Pseudoscorpiones) of northern Arizona, with the description of two new short-range endemic species

This study reports on the pseudoscorpion fauna of the subterranean ecosystems of northern Arizona, U.S.A. Our work resulted in the descriptions of two new species, Hesperochernes bradybaughi sp. nov. and Tuberochernes cohni sp. nov. (Chernetidae) and the range expansion of one species, Larca cavicola (Muchmore 1981) (Larcidae). All of these species were cave-adapted and found within caves on Grand Canyon-Parashant National Monument in northwestern Arizona. Based upon this work, the genus Archeolarca Hoff and Clawson is newly synonymized with Larca Chamberlin, and the following species are transferred from Archeolarca to Larca, forming the new combinations L. aalbui (Muchmore 1984), L. cavicola (Muchmore 1981), L. guadalupensis (Muchmore 1981) and L. welbourni (Muchmore 1981). Despite intensive sampling on the monument, the two new species were detected in only one cave. This cave supports the greatest diversity of troglomorphic arthropod species on the monument—all of which are short-range endemics occurring in only one cave. Maintaining the management recommendations provided by Peck and Wynne (2013) for this cave should aid in the long-term persistence of these new pseudoscorpion species, as well as the other troglomorphic arthropods

The Schizosaccharomyces pombe Aurora–related Kinase Ark1 Interacts with the Inner Centromere Protein Pic1 and Mediates Chromosome Segregation and Cytokinesis

The chromosomal passenger proteins aurora-B, survivin, and inner centromere protein (INCENP) have been implicated in coordinating chromosome segregation with cell division. This work describes the interplay between aurora, survivin, and INCENP orthologs in the fission yeast Schizosaccharomyces pombe and defines their roles in regulating chromosome segregation and cytokinesis. We describe the cloning and characterization of the aurora-related kinase gene ark1(+), demonstrating that it is an essential gene required for sister chromatid segregation. Cells lacking Ark1p exhibit the cut phenotype, DNA fragmentation, and other defects in chromosome segregation. Overexpression of a kinase-defective version of Ark1, Ark1-K147R, inhibits cytokinesis, with cells exhibiting an elongated, multiseptate phenotype. Ark1p interacts physically and/or genetically with the survivin and INCENP orthologs Bir1p and Pic1p. We identified Pic1p in a two-hybrid screen for Ark1-K147R interacting partners and went on to map domains in both proteins that mediate their binding. Pic1p residues 925–972 are necessary and sufficient for Ark1p binding, which occurs through the kinase domain. As with Ark1-K147R, overexpression of Ark1p-binding fragments of Pic1p leads to multiseptate phenotypes. We also provide evidence that the dominant-negative effect of Ark1-K147R requires Pic1p binding, indicating that the formation of Ark1p-Pic1p complexes is required for the execution of cytokinesis