Jerome C Nwachukwu

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During the stress response to intense exercise, the sympathetic nervous system (SNS) induces rapid catabolism of energy reserves through the release of catecholamines and subsequent activation of protein kinase A (PKA). Paradoxically, chronic administration of sympathomimetic drugs (β-agonists) leads to anabolic adaptations in skeletal muscle, suggesting(More)
Resveratrol has beneficial effects on aging, inflammation and metabolism, which are thought to result from activation of the lysine deacetylase, sirtuin 1 (SIRT1), the cAMP pathway, or AMP-activated protein kinase. In this study, we report that resveratrol acts as a pathway-selective estrogen receptor-α (ERα) ligand to modulate the inflammatory response but(More)
Ligand-binding dynamics control allosteric signaling through the estrogen receptor-α (ERα), but the biological consequences of such dynamic binding orientations are unknown. Here, we compare a set of ER ligands having dynamic binding orientation (dynamic ligands) with a control set of isomers that are constrained to bind in a single orientation (constrained(More)
c-Jun N-terminal (JNK) family kinases have a common peptide-docking site used by upstream activating kinases, substrates, scaffold proteins, and phosphatases, where the ensemble of bound proteins determines signaling output. Although there are many JNK structures, little is known about mechanisms of allosteric regulation between the catalytic and(More)
To develop estrogen receptor (ER) ligands having novel structures and activities, we have explored compounds in which the central hydrophobic core has a more three-dimensional topology than typically found in estrogen ligands and thus exploits the unfilled space in the ligand-binding pocket. Here, we build upon our previous investigations of(More)
We have explored the isoelectronic replacement of the C═C double bond found at the core of many nonsteroidal estrogen ligands with a simple Schiff base (C═N). Di- and triaryl-substituted imine derivatives were conveniently prepared by the condensation of benzophenones with various anilines without the need for phenolic hydroxy protection. Most of these(More)
Nuclear receptors (NRs) can be conceptualized as highly dynamic scaffold proteins, where binding of ligand, DNA or transcriptional coregulator proteins can allosterically change the scaffold structure and direct changes in subsequent binding events. In this issue of The EMBO Journal, Orlov et al present the first cryo-EM structure of a NR complex, a(More)
A subset of nuclear receptors (NRs) function as obligate heterodimers with retinoid X receptor (RXR), allowing integration of ligand-dependent signals across the dimer interface via an unknown structural mechanism. Using nuclear magnetic resonance (NMR) spectroscopy, x-ray crystallography and hydrogen/deuterium exchange (HDX) mass spectrometry, here we show(More)
The paper highlights Quality related Costs and how the costs can be extracted from an industry’s manufacturing and financial records. The level of automation of industrial manufacturing systems was measured and interfaced with quality-related cost. The significance of the relationship between the two important industrial parameters was evaluated. The(More)
Previously, we discovered estrogen receptor (ER) ligands with a novel three-dimensional oxabicyclo[2.2.1]heptene core scaffold and good ER binding affinity act as partial agonists via small alkyl ester substitutions on the bicyclic core that indirectly modulate the critical switch helix in the ER ligand binding domain, helix 12, by interactions with helix(More)