Abstract

This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Allosteric communication between remote sites is a crucial element in enzymatic function. Using TROSY-based NMR spectroscopy, we will map long-range allosteric changes along the backbone of the catalytic subunit of cAMP-dependent protein kinase A (PKA) upon binding a nucleotide analogue (AMP-PNP) and the peptide LRRASLG (Kemptide) as substrates. Calculations for the binding constants of the two ligands, as well as for on and off rates will be obtained. Since the enzyme retains activity under our NMR conditions, the structural changes monitored in this study will reflect the interconversion of conformations during turnover. These studies represent a paradigm for how multidomain kinase turnover involves complex dynamics transmitted within its structure. In addition, this is the first report of monitored dynamic changes within an active kinase at atomic resolution.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR002301-23
Application #
7721636
Study Section
Special Emphasis Panel (ZRG1-BCMB-E (40))
Project Start
2008-03-01
Project End
2009-02-28
Budget Start
2008-03-01
Budget End
2009-02-28
Support Year
23
Fiscal Year
2008
Total Cost
$7,757
Indirect Cost

  Institution

Name
University of Wisconsin Madison
Department
Biochemistry
Type
Schools of Earth Sciences/Natur
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715

  Publications

Travers, Timothy; López, Cesar A; Van, Que N et al. (2018) Molecular recognition of RAS/RAF complex at the membrane: Role of RAF cysteine-rich domain. Sci Rep 8:8461
Thomas, Nathan E; Wu, Chao; Morrison, Emma A et al. (2018) The C terminus of the bacterial multidrug transporter EmrE couples drug binding to proton release. J Biol Chem 293:19137-19147
Assadi-Porter, Fariba M; Radek, James; Rao, Hongyu et al. (2018) Multimodal Ligand Binding Studies of Human and Mouse G-Coupled Taste Receptors to Correlate Their Species-Specific Sweetness Tasting Properties. Molecules 23:
Wijayatunga, Nadeeja N; Sams, Valerie G; Dawson, John A et al. (2018) Roux-en-Y gastric bypass surgery alters serum metabolites and fatty acids in patients with morbid obesity. Diabetes Metab Res Rev 34:e3045
Assadi-Porter, Fariba M; Reiland, Hannah; Sabatini, Martina et al. (2018) Metabolic Reprogramming by 3-Iodothyronamine (T1AM): A New Perspective to Reverse Obesity through Co-Regulation of Sirtuin 4 and 6 Expression. Int J Mol Sci 19:
Dominguez, Eddie; Zarnowski, Robert; Sanchez, Hiram et al. (2018) Conservation and Divergence in the Candida Species Biofilm Matrix Mannan-Glucan Complex Structure, Function, and Genetic Control. MBio 9:
Franco, Aldo; Dovell, Sanaz; Möller, Carolina et al. (2018) Structural plasticity of mini-M conotoxins - expression of all mini-M subtypes by Conus regius. FEBS J 285:887-902
Wales, Jessica A; Chen, Cheng-Yu; Breci, Linda et al. (2018) Discovery of stimulator binding to a conserved pocket in the heme domain of soluble guanylyl cyclase. J Biol Chem 293:1850-1864
Selen Alpergin, Ebru S; Bolandnazar, Zeinab; Sabatini, Martina et al. (2017) Metabolic profiling reveals reprogramming of lipid metabolic pathways in treatment of polycystic ovary syndrome with 3-iodothyronamine. Physiol Rep 5:
Mong, Surin K; Cochran, Frank V; Yu, Hongtao et al. (2017) Heterochiral Knottin Protein: Folding and Solution Structure. Biochemistry 56:5720-5725

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