Abstract

Two important monooxygenase enzymes, dopamine-b-hydroxylase (DBH) and peptidylglycine hydroxylating monooxygenase (PHM) are involved in the biosynthesis of neurotransmitters and peptide hormones, and are thus of pivotal importance in cell signalling mechanisms, and neuroregulatory function. The research is focussed toward elucidating the coordination chemistry of the Cu(I) forms of the enzymes, at which dioxygen-binding and substrate hydroxylation occur. Novel methodologies involving binding of Cu(I)-specific ligands such as CO and isocyanides will be developed as powerful probes of Cu(I) structure and substitution chemistry. Site directed mutants of PHM will also be studied in order to test current models of active-site structure.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR001209-17
Application #
5222809
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
17
Fiscal Year
1996
Total Cost
Indirect Cost

  Publications

Vickers, Chelsea; Liu, Feng; Abe, Kento et al. (2018) Endo-fucoidan hydrolases from glycoside hydrolase family 107 (GH107) display structural and mechanistic similarities to ?-l-fucosidases from GH29. J Biol Chem 293:18296-18308
Nguyen, Phong T; Lai, Jeffrey Y; Lee, Allen T et al. (2018) Noncanonical role for the binding protein in substrate uptake by the MetNI methionine ATP Binding Cassette (ABC) transporter. Proc Natl Acad Sci U S A 115:E10596-E10604
Aleman, Fernando; Tzarum, Netanel; Kong, Leopold et al. (2018) Immunogenetic and structural analysis of a class of HCV broadly neutralizing antibodies and their precursors. Proc Natl Acad Sci U S A 115:7569-7574
Herrera, Nadia; Maksaev, Grigory; Haswell, Elizabeth S et al. (2018) Elucidating a role for the cytoplasmic domain in the Mycobacterium tuberculosis mechanosensitive channel of large conductance. Sci Rep 8:14566
Lal, Neeraj K; Nagalakshmi, Ugrappa; Hurlburt, Nicholas K et al. (2018) The Receptor-like Cytoplasmic Kinase BIK1 Localizes to the Nucleus and Regulates Defense Hormone Expression during Plant Innate Immunity. Cell Host Microbe 23:485-497.e5
Pluvinage, Benjamin; Grondin, Julie M; Amundsen, Carolyn et al. (2018) Molecular basis of an agarose metabolic pathway acquired by a human intestinal symbiont. Nat Commun 9:1043
Beyerlein, Kenneth R; Jönsson, H Olof; Alonso-Mori, Roberto et al. (2018) Ultrafast nonthermal heating of water initiated by an X-ray Free-Electron Laser. Proc Natl Acad Sci U S A 115:5652-5657
Yoshizawa, Takuya; Ali, Rustam; Jiou, Jenny et al. (2018) Nuclear Import Receptor Inhibits Phase Separation of FUS through Binding to Multiple Sites. Cell 173:693-705.e22
Noach, Ilit; Ficko-Blean, Elizabeth; Pluvinage, Benjamin et al. (2017) Recognition of protein-linked glycans as a determinant of peptidase activity. Proc Natl Acad Sci U S A 114:E679-E688
Robb, Melissa; Hobbs, Joanne K; Woodiga, Shireen A et al. (2017) Molecular Characterization of N-glycan Degradation and Transport in Streptococcus pneumoniae and Its Contribution to Virulence. PLoS Pathog 13:e1006090

Showing the most recent 10 out of 604 publications