The NYSGRC has a 10-year proven track record in high-throughput structure determination as well as in discovering and innplementing infrastructure to increase the speed, accuracy, success rate and affordability of structural biology studies. Moving forward the NYSGRC will reorganize to meet the new and diverse challenges associated with the PSI:Biology Network. In addition to reliance on traditional high-throughput bacterial expression platforms, the NYSGRC will develop and implement cutting-edge experimental and computational technologies to examine the biologically important molecules that are the focus of PShBiology. These targets are likely to include multidomain eukaryotic proteins, multi-component assemblies, and secreted proteins that underly complex multi-cellular biology and directly contribute to human health and disease. In addition to servicing the High-Throughput-Enabled Structural Biology Partnerships, this infrastructure will support our Biological Theme that focuses on the secretion machinery and secreted effector proteins from major bacterial, protozoan and fungal pathogens. These targets were specifically selected to provide new insights into the mechanisms that these pathogens have evolved for immune evasion and modulation of host signaling pathways. These processes rely on intricate nanomachines, with cytoplasmic, membrane-associated and extracellular components, that require hybrid computational and experimental approaches to define their organization, structure and function. Finally, our integrated experimental and computational efforts have identified new opportunities to significantly and economically enhance sequence/structure coverage. The advent of PShBiology is driving a process of evolutionary change for the NYSGRC that has already enhanced its outstanding high-throughput structure determination pipeline. Our stengths in traditional bacterial expression, coupled with novel approaches to eukaryotic expression and refolding, as well as our established expertise in hybrid methods, postions us to uniquely support the efforts of PShBiology.
The NIH is oommited to advancing research directly relevant to a detailed understanding of human health and disease states. The research proposed in this application is designed to significantly enhance the ability of the scientific community to define the shapes and structures of important macromolecules. This information provides enormous insights into strategies to develop drugs and therapetics to combat infectious diseases, autoirhmune diseases and cancers.
|Jing, Yang; Kumar, P Rajesh; Zhu, Lei et al. (2014) Novel decorin mutation in a Chinese family with congenital stromal corneal dystrophy. Cornea 33:288-93|
|Padlan, Camille S; Malashkevich, Vladimir N; Almo, Steve C et al. (2014) An RNA aptamer possessing a novel monovalent cation-mediated fold inhibits lysozyme catalysis by inhibiting the binding of long natural substrates. RNA 20:447-61|
|Hobbs, Merlin Eric; Williams, Howard J; Hillerich, Brandan et al. (2014) l-Galactose metabolism in Bacteroides vulgatus from the human gut microbiota. Biochemistry 53:4661-70|
|Zheng, Heping; Hou, Jing; Zimmerman, Matthew D et al. (2014) The future of crystallography in drug discovery. Expert Opin Drug Discov 9:125-37|
|Almo, Steven C; Love, James D (2014) Better and faster: improvements and optimization for mammalian recombinant protein production. Curr Opin Struct Biol 26:39-43|
|Wichelecki, Daniel J; Graff, Dylan C; Al-Obaidi, Nawar et al. (2014) Identification of the in vivo function of the high-efficiency D-mannonate dehydratase in Caulobacter crescentus NA1000 from the enolase superfamily. Biochemistry 53:4087-9|
|Koellhoffer, Jayne F; Dai, Zhou; Malashkevich, Vladimir N et al. (2014) Structural characterization of the glycoprotein GP2 core domain from the CAS virus, a novel arenavirus-like species. J Mol Biol 426:1452-68|
|Higgins, Chelsea D; Malashkevich, Vladimir N; Almo, Steven C et al. (2014) Influence of a heptad repeat stutter on the pH-dependent conformational behavior of the central coiled-coil from influenza hemagglutinin HA2. Proteins 82:2220-8|
|Tsou, Wen-I; Nguyen, Khanh-Quynh N; Calarese, Daniel A et al. (2014) Receptor tyrosine kinases, TYRO3, AXL, and MER, demonstrate distinct patterns and complex regulation of ligand-induced activation. J Biol Chem 289:25750-63|
|Wichelecki, Daniel J; Vendiola, Jean Alyxa Ferolin; Jones, Amy M et al. (2014) Investigating the physiological roles of low-efficiency D-mannonate and D-gluconate dehydratases in the enolase superfamily: pathways for the catabolism of L-gulonate and L-idonate. Biochemistry 53:5692-9|
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