Church, W. Bret - University of Sydney

研究领域

My interests are in structure-based drug design and particularly the use of biophysical techniques, structural biology and structural bioinformatics to help understand the relationships between drug targets and drugs to be applied to drug discovery. Abnormal levels of kynurenic acid (KA) have been thought to accompany several neuropsychiatric diseases, especially schizophrenia. This is consistent with the role of KA as an antagonist acting at the glutamate-binding site of the N-methyl D-aspartic acid receptor. Production of this metabolite by kynurenine aminotransferases could contribute to pathophysiology of psychoses, making the kynurenine pathway a valuable target for the treatment of such diseases. On this basis, novel inhibitors of the human kynurenine aminotransferases will be valuable, and we have been pursuing their design. Over 700 depositions to the data bank holding protein structures are made every month. Each entry may be a new structure, a structure with a new inhibitor or a mutant. These structures are providing more data in the quest for realistic assessments of molecular recognition and interaction, which are the basis for all cellular processes, and therefore of great interest for studies in therapeutic intervention. We are interested in the analysis of available protein structures to further prediction methods. Of great importance have been recent protein structures such as the adrenergic, dopamine and histamine receptors, representing the first of the highly resolved G-protein coupled receptor structures. Areas of specific interest are the G-protein coupled receptors, but also other membrane-bound targets. With an understanding of genomic sequencing, automated tools may be a way to expedite the pipeline directly from the potential drug targets to the discovery of drug candidates.

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Nematollahi, A., Sun, G., Jayawickrama, G., Church, W. (2016). Kynurenine aminotransferase isozyme inhibitors: A review. International Journal of Molecular Sciences, 17(6), 1-22. [More Information] Nematollahi, A., Sun, G., Harrop, S., Hanrahan, J., Church, W. (2016). Structure of the PLP-Form of the Human Kynurenine Aminotransferase II in a Novel Spacegroup at 1.83 A Resolution. International Journal of Molecular Sciences, 17(4), 1-11. [More Information] Nematollahi, A., Sun, G., Jayawickrama, G., Hanrahan, J., Church, W. (2016). Study of the Activity and Possible Mechanism of Action of a Reversible Inhibitor of Recombinant Human KAT-2: A Promising Lead in Neurodegenerative and Cognitive Disorders. Molecules, 21(7), 1-9. [More Information] Lynch, G., Portelli, S., Church, W. (2015). Composite Model of Full GP Structure of Ebola Virus Envelope Glycoprotein. Journal of Molecular and Genetic Medicine, 9, 1-4. [More Information] Jayawickrama, G., Sadig, R., Sun, G., Nematollahi, A., Nadvi, N., Hanrahan, J., Gorrell, M., Church, W. (2015). Kynurenine aminotransferases and the prospects of inhibitors for the treatment of schizophrenia. Current Medicinal Chemistry, 22(24), 2902-2918. [More Information] Kim, E., Rath, E., Tsang, V., Duff, A., Robinson, B., Church, W., Benn, D., Dwight, T., Clifton-Bligh, R. (2015). Structural and functional consequences of succinate dehydrogenase subunit B mutations. Endocrine-Related Cancer, 22(3), 387-397. [More Information] Nematollahi, A., Aminimoghadamfarouj, N., Church, W. (2014). Essential structural features of novel antischizophrenic drugs: a review. Medicinal Chemistry, 10(6), 541-549. [More Information] Nematollahi, A., Church, W., Nadvi, N., Gorrell, M., Sun, G. (2014). Homology Modeling of Human Kynurenine Aminotransferase III and Observations on Inhibitor Binding Using Molecular Docking. Central Nervous System Agents in Medicinal Chemistry, 14(1), 2-9. [More Information] Tessier, D., Laroum, S., Duval, B., Rath, E., Church, W., Hao, J. (2014). In silico evaluation of the influence of the translocon on partitioning of membrane segments. BMC Bioinformatics, 15(156). [More Information] Rath, E., Duff, A., Håkansson, A., Knott, R., Church, W. (2014). Small-angle X-ray scattering of BAMLET at pH 12: A complex of α-lactalbumin and oleic acid. Proteins: Structure, Function, and Bioinformatics, 82(7), 1400-1408. [More Information] Lee, H., Lee, H., Lee, L., Teber, E., Church, W. (2014). The use of soluble protein structures in modeling helical proteins in a layered membrane. Journal of Biomolecular Structure & Dynamics, 32(2), 308-318. [More Information] Rath, E., Tessier, D., Campbell, A., Lee, H., Werner, T., Salam, N., Lee, L., Church, W. (2013). A benchmark server using high resolution protein structure data, and benchmark results for membrane helix predictions. BMC Bioinformatics, 14(1), 1-11. [More Information] Zhou, F., Zheng, J., Zhu, L., Jodal, A., Cui, P., Wong, K., Gurney, H., Church, W., Murray, M. (2013). Functional Analysis of Novel Polymorphisms in the Human SLCO1A2 Gene that Encodes the Transporter OATP1A2. The AAPS Journal, 15(4), 1099-1108. [More Information] Werner, T., Church, W. (2013). Kink characterization and modeling in transmembrane protein structures. Journal of Chemical Information and Modeling, 53(11), 2926-2936. [More Information] Hamzeh-Mivehroud, M., Alizadeh, A., Morris, M., Church, W., Dastmalchi, S. (2013). Phage display as a technology delivering on the promise of peptide drug discovery. Drug Discovery Today, 18(23-24), 1144-1157. [More Information] Lee, L., Bryant, K., Bouveret, R., Lei, P., Duff, A., Harrop, S., Huang, E., Harvey, R., Gelb, M., Gray, P., Church, W., et al (2013). Selective Inhibition of Human Group IIA-secreted Phospholipase a 2 (hGIIA) Signaling Reveals Arachidonic Acid Metabolism Is Associated with Colocalization of hGIIA to Vimentin in Rheumatoid Synoviocytes. Journal of Biological Chemistry, 288(21), 15269-15279. [More Information] Akladios, F., Nadvi, N., Park, J., Hanrahan, J., Kapoor, V., Gorrell, M., Church, W. (2012). Design and synthesis of novel inhibitors of human kynurenine aminotransferase-I. Bioorganic & Medicinal Chemistry Letters, 22(4), 1579-1581. [More Information] Lynch, G., Selleck, P., Church, W., Sullivan, J. (2012). Seasoned adaptive antibody immunity for highly pathogenic pandemic influenza in humans. Immunology and Cell Biology, 90(2), 149-158. [More Information] Werner, T., Morris, M., Dastmalchi, S., Church, W. (2012). Structural modelling and dynamics of proteins for insights into drug interactions. Advanced Drug Delivery Reviews, 64(4), 323-343. [More Information] Bryant, K., Bidgood, M., Lei, P., Taberner, M., Salom, C., Kumar, V., Lee, L., Church, W., Courtenay, B., Smart, B., et al (2011). A Bifunctional Role for Group IIA Secreted Phospholipase A2 in Human Rheumatoid Fibroblast-like Synoviocyte Arachidonic Acid Metabolism. Journal of Biological Chemistry, 286(4), 2492-2503. [More Information]