Abstract

Protein kinases constitute a large and diverse family of enzymes. One member is the catalytic (C) subunit of cyclic adenosine monophosphate (cAMP) dependent protein kinase (cAPK). In the absence of cAMP, the enzyme is sequestered as an inactive tetrameric complex containing both regulatory (R) and catalytic subunits. Upon binding of cAMP, the holoenzyme (R2C2) dissociates into an R-cAMP dimer and two active, monomeric C subunits. Recently, we have solved structures of the rC-subunit complexed with adenosine and for the first time without peptide inhibitor. Also, we have solved the structure of the rC-subunit with a potent natural product inhibitor. These structures are beginning to lay the basis for structure based drug design. The structure solution of this apo form would greatly enhance our knowledge on the domain movements, protein conformational changes and also give better starting points for drug design.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
3P41RR001209-23S1
Application #
6658704
Study Section
Project Start
2002-03-01
Project End
2003-02-28
Budget Start
Budget End
Support Year
23
Fiscal Year
2002
Total Cost
$143,176
Indirect Cost

  Institution

Name
Stanford University
Department
Type
DUNS #
800771545
City
Stanford
State
CA
Country
United States
Zip Code
94305

  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
Feinberg, Hadar; Jégouzo, Sabine A F; Rex, Maximus J et al. (2017) Mechanism of pathogen recognition by human dectin-2. J Biol Chem 292:13402-13414
Warelow, Thomas P; Pushie, M Jake; Cotelesage, Julien J H et al. (2017) The active site structure and catalytic mechanism of arsenite oxidase. Sci Rep 7:1757

Showing the most recent 10 out of 604 publications