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Amino Acids, Peptides, and Proteins Commons™

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Enzymes and Coenzymes

2014

Articles 1 - 3 of 3

Full-Text Articles in Amino Acids, Peptides, and Proteins

Synchronous Opening And Closing Motions Are Essential For Camp-Dependent Protein Kinase A Signaling, Atul K. Srivastava, Leanna R. Mcdonald, Alessandro Cembran, Jonggul Kim, Larry R. Masterson, Christopher L. Mcclendon, Susan S. Taylor, Gianluigi Veglia Nov 2014

Synchronous Opening And Closing Motions Are Essential For Camp-Dependent Protein Kinase A Signaling, Atul K. Srivastava, Leanna R. Mcdonald, Alessandro Cembran, Jonggul Kim, Larry R. Masterson, Christopher L. Mcclendon, Susan S. Taylor, Gianluigi Veglia

Larry Masterson

Conformational fluctuations play a central role in enzymatic catalysis. However, it is not clear how the rates and the coordination of the motions affect the different catalytic steps. Here, we used NMR spectroscopy to analyze the conformational fluctuations of the catalytic subunit of the cAMP-dependent protein kinase (PKA-C), a ubiquitous enzyme involved in a myriad of cell signaling events. We found that the wild-type enzyme undergoes synchronous motions involving several structural elements located in the small lobe of the kinase, which is responsible for nucleotide binding and release. In contrast, a mutation (Y204A) located far from the active site desynchronizes the opening and …

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Mechanism Underlying Ikk Activation Mediated By The Linear Ubiquitin Chain Assembly Complex (Lubac), Hiroaki Fujita, Simin Rahighi, Mariko Akita, Ryuichi Kato, Yoshiteru Sasaki, Soichi Wakatsuki, Kazuhiro Iwai Apr 2014

Mechanism Underlying Ikk Activation Mediated By The Linear Ubiquitin Chain Assembly Complex (Lubac), Hiroaki Fujita, Simin Rahighi, Mariko Akita, Ryuichi Kato, Yoshiteru Sasaki, Soichi Wakatsuki, Kazuhiro Iwai

Pharmacy Faculty Articles and Research

The linear ubiquitin chain assembly complex (LUBAC) ligase, consisting of HOIL-1L, HOIP, and SHARPIN, specifically generates linear polyubiquitin chains. LUBAC-mediated linear polyubiquitination has been implicated in NF-κB activation. NEMO, a component of the IκB kinase (IKK) complex, is a substrate of LUBAC, but the precise molecular mechanism underlying linear chain-mediated NF-κB activation has not been fully elucidated. Here, we demonstrate that linearly polyubiquitinated NEMO activates IKK more potently than unanchored linear chains. In mutational analyses based on the crystal structure of the complex between the HOIP NZF1 and NEMO CC2-LZ domains, which are involved in the HOIP-NEMO interaction, NEMO mutations …

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The Development Of A Synthetic Route For A Disubsitituted Diphenylacetylene And Its Conformational Characteristics Upon Coordination To Tungsten: A Prospect For Beta-Sheet Studies, Francis Herman Apr 2014

The Development Of A Synthetic Route For A Disubsitituted Diphenylacetylene And Its Conformational Characteristics Upon Coordination To Tungsten: A Prospect For Beta-Sheet Studies, Francis Herman

Senior Theses and Projects

The study of β-sheet mimetics represents an important step in understanding the structural and function of β-sheets. The purpose of this report was to develop a β-sheet mimetic through a diphenylacetylene backbone, coordinate the complex to tungsten and determine the structural and conformational characteristics of the complex. In order to characterize the different compounds ESI-MS, 1HNMR, COSY NMR, NOESY NMR, and ROESY NMR were employed. The diphenylacetylene backbone contained two phenyl substituents with a peptide chain of two amino acids. The β-sheet mimetic 1 was successfully synthesized utilizing peptide coupling reactions and a Sonogashira coupling reaction. Previous research by …

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