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Biochemistry, Biophysics, and Structural Biology Commons

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Full-Text Articles in Biochemistry, Biophysics, and Structural Biology

Intra-Domain Cross-Talk Regulates Serine-Arginine Protein Kinase 1-Dependent Phosphorylation And Splicing Function Of Transformer 2Β1, Michael A. Jamros, Brandon E. Aubol, Malik M. Keshwani, Zhaiyi Zhang, Stefan Stamm, Joseph A. Adams Jul 2015

Intra-Domain Cross-Talk Regulates Serine-Arginine Protein Kinase 1-Dependent Phosphorylation And Splicing Function Of Transformer 2Β1, Michael A. Jamros, Brandon E. Aubol, Malik M. Keshwani, Zhaiyi Zhang, Stefan Stamm, Joseph A. Adams

Molecular and Cellular Biochemistry Faculty Publications

Transformer 2β1 (Tra2β1) is a splicing effector protein composed of a core RNA recognition motif flanked by two arginine-serine-rich (RS) domains, RS1 and RS2. Although Tra2β1-dependent splicing is regulated by phosphorylation, very little is known about how protein kinases phosphorylate these two RS domains. We now show that the serine-arginine protein kinase-1 (SRPK1) is a regulator of Tra2β1 and promotes exon inclusion in the survival motor neuron gene 2 (SMN2). To understand how SRPK1 phosphorylates this splicing factor, we performed mass spectrometric and kinetic experiments. We found that SRPK1 specifically phosphorylates 21 serines in RS1, a process facilitated …


Molecular Effects Of Cancer-Associated Somatic Mutations On The Structural And Target Recognition Properties Of Keap1., Halema Khan, Ryan C Killoran, Anne Brickenden, Jingsong Fan, Daiwen Yang, Wing-Yiu Choy Apr 2015

Molecular Effects Of Cancer-Associated Somatic Mutations On The Structural And Target Recognition Properties Of Keap1., Halema Khan, Ryan C Killoran, Anne Brickenden, Jingsong Fan, Daiwen Yang, Wing-Yiu Choy

Biochemistry Publications

Kelch-like ECH-associated protein 1 (Keap1) plays an important regulatory role in the nuclear factor erythroid 2-related factor 2 (Nrf2)-dependent oxidative stress response pathway. It functions as a repressor of Nrf2, a key transcription factor that initiates the expression of cytoprotective enzymes during oxidative stress to protect cells from damage caused by reactive oxygen species. Recent studies show that mutations of Keap1 can lead to aberrant activation of the antioxidant pathway, which is associated with different types of cancers. To gain a mechanistic understanding of the links between Keap1 mutations and cancer pathogenesis, we have investigated the molecular effects of a …


Ph Dependence Of Cyanide And Imidazole Binding To The Heme Domains Of Sinorhizobium Meliloti And Bradyrhizobium Japonicum Fixl, Anil K. Bidwai, Angela J. Ahrendt, John S. Sullivan, Lidia B. Vitello, James E. Erman Jan 2015

Ph Dependence Of Cyanide And Imidazole Binding To The Heme Domains Of Sinorhizobium Meliloti And Bradyrhizobium Japonicum Fixl, Anil K. Bidwai, Angela J. Ahrendt, John S. Sullivan, Lidia B. Vitello, James E. Erman

Faculty Publications & Research

Equilibrium and kinetic properties of cyanide and imidazole binding to the heme domains of Sinorhizobium meliloti and Bradyrhizobium japonicum FixL (SmFixLH and BjFixLH) have been investigated between pH 5 and 11. KD determinations were made at integral pH values, with the strongest binding at pH 9 for both ligands. KD for the cyanide complexes of BjFixLH and SmFixLH is 0.15 ± 0.09 and 0.50 ± 0.20 μM, respectively, and 0.70 ± 0.01 mM for imido-BjFixLH. The association rate constants are pH dependent with maximum values of 443 ± 8 and 252 ± 61 …