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Dive into the research topics where April Case is active.

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Featured researches published by April Case.


Journal of Biological Chemistry | 2010

SIRT1 activation by small molecules - kinetic and biophysical evidence for direct interaction of enzyme and activator

Han Dai; Lauren Kustigian; David Carney; April Case; Thomas Considine; Basil P. Hubbard; Robert B. Perni; Thomas V. Riera; Bruce Szczepankiewicz; George P. Vlasuk; Ross L. Stein

SIRT1 is a protein deacetylase that has emerged as a therapeutic target for the development of activators to treat diseases of aging. SIRT1-activating compounds (STACs) have been developed that produce biological effects consistent with direct SIRT1 activation. At the molecular level, the mechanism by which STACs activate SIRT1 remains elusive. In the studies reported herein, the mechanism of SIRT1 activation is examined using representative compounds chosen from a collection of STACs. These studies reveal that activation of SIRT1 by STACs is strongly dependent on structural features of the peptide substrate. Significantly, and in contrast to studies reporting that peptides must bear a fluorophore for their deacetylation to be accelerated, we find that some STACs can accelerate the SIRT1-catalyzed deacetylation of specific unlabeled peptides composed only of natural amino acids. These results, together with others of this study, are at odds with a recent claim that complex formation between STACs and fluorophore-labeled peptides plays a role in the activation of SIRT1 (Pacholec, M., Chrunyk, B., Cunningham, D., Flynn, D., Griffith, D., Griffor, M., Loulakis, P., Pabst, B., Qiu, X., Stockman, B., Thanabal, V., Varghese, A., Ward, J., Withka, J., and Ahn, K. (2010) J. Biol. Chem. 285, 8340–8351). Rather, the data suggest that STACs interact directly with SIRT1 and activate SIRT1-catalyzed deacetylation through an allosteric mechanism.


Nature Communications | 2015

Crystallographic structure of a small molecule SIRT1 activator-enzyme complex.

Han Dai; April Case; Thomas V. Riera; Thomas Considine; Jessica E. Lee; Yoshitomo Hamuro; Huizhen Zhao; Yong Jiang; Sharon Sweitzer; Beth Pietrak; Benjamin J. Schwartz; Charles A. Blum; Jeremy S. Disch; Richard Caldwell; Bruce G. Szczepankiewicz; Christopher Oalmann; Pui Yee Ng; Brian H. White; Rebecca L. Casaubon; Radha Narayan; Karsten Koppetsch; Francis Bourbonais; Bo Wu; Junfeng Wang; Dongming Qian; Fan Jiang; Cheney Mao; Minghui Wang; Erding Hu; Joseph Wu

SIRT1, the founding member of the mammalian family of seven NAD+-dependent sirtuins, is composed of 747 amino acids forming a catalytic domain and extended N- and C-terminal regions. We report the design and characterization of an engineered human SIRT1 construct (mini-hSIRT1) containing the minimal structural elements required for lysine deacetylation and catalytic activation by small molecule sirtuin-activating compounds (STACs). Using this construct, we solved the crystal structure of a mini-hSIRT1-STAC complex, which revealed the STAC-binding site within the N-terminal domain of hSIRT1. Together with hydrogen-deuterium exchange mass spectrometry (HDX-MS) and site-directed mutagenesis using full-length hSIRT1, these data establish a specific STAC-binding site and identify key intermolecular interactions with hSIRT1. The determination of the interface governing the binding of STACs with human SIRT1 facilitates greater understanding of STAC activation of this enzyme, which holds significant promise as a therapeutic target for multiple human diseases.


Bioorganic & Medicinal Chemistry Letters | 2009

Structure–activity relationship study of EphB3 receptor tyrosine kinase inhibitors

Lixin Qiao; Sungwoon Choi; April Case; Thomas G. Gainer; Kathleen Seyb; Marcie A. Glicksman; Donald C. Lo; Ross L. Stein; Gregory D. Cuny

A structure-activity relationship study for a 2-chloroanilide derivative of pyrazolo[1,5-a]pyridine revealed that increased EphB3 kinase inhibitory activity could be accomplished by retaining the 2-chloroanilide and introducing a phenyl or small electron donating substituents to the 5-position of the pyrazolo[1,5-a]pyridine. In addition, replacement of the pyrazolo[1,5-a]pyridine with imidazo[1,2-a]pyridine was well tolerated and resulted in enhanced mouse liver microsome stability. The structure-activity relationship for EphB3 inhibition of both heterocyclic series was similar. Kinase inhibitory activity was also demonstrated for representative analogs in cell culture. An analog (32, LDN-211904) was also profiled for inhibitory activity against a panel of 288 kinases and found to be quite selective for tyrosine kinases. Overall, these studies provide useful molecular probes for examining the in vitro, cellular and potentially in vivo kinase-dependent function of EphB3 receptor.


Chemistry & Biology | 2003

Discovery of inhibitors that elucidate the role of UCH-L1 activity in the H1299 lung cancer cell line

Yichin Liu; Hilal A. Lashuel; Sungwoon Choi; Xuechao Xing; April Case; Jake Ni; Li-An Yeh; Gregory D. Cuny; Ross L. Stein; Peter T. Lansbury


Bioorganic & Medicinal Chemistry Letters | 2005

Structure-activity relationship study of novel tissue transglutaminase inhibitors

Eric Duval; April Case; Ross L. Stein; Gregory D. Cuny


Bioorganic & Medicinal Chemistry Letters | 2007

Structure–activity relationship, kinetic mechanism, and selectivity for a new class of ubiquitin C-terminal hydrolase-L1 (UCH-L1) inhibitors

Ara H. Mermerian; April Case; Ross L. Stein; Gregory D. Cuny


Biochemistry | 2003

Mechanistic origins of the substrate selectivity of serine proteases.

April Case; Ross L. Stein


Biochemistry | 2007

Kinetic analysis of the interaction of tissue transglutaminase with a nonpeptidic slow-binding inhibitor.

April Case; Ross L. Stein


Biochemistry | 2003

Kinetic analysis of the action of tissue transglutaminase on peptide and protein substrates.

April Case; Ross L. Stein


Analytical Biochemistry | 2005

Development of a mechanism-based assay for tissue transglutaminase--results of a high-throughput screen and discovery of inhibitors.

April Case; Jake Ni; Li-An Yeh; Ross L. Stein

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Ross L. Stein

Brigham and Women's Hospital

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Eric Duval

Brigham and Women's Hospital

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Marcie A. Glicksman

Brigham and Women's Hospital

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Sungwoon Choi

Brigham and Women's Hospital

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