Joseph E. Tropea
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View article: <scp>P1</scp>′ specificity of the <scp>S219V</scp>/<scp>R203G</scp> mutant tobacco etch virus protease
<span>P1</span>′ specificity of the <span>S219V</span>/<span>R203G</span> mutant tobacco etch virus protease Open
Proteases that recognize linear amino acid sequences with high specificity became indispensable tools of recombinant protein technology for the removal of various fusion tags. Due to its stringent sequence specificity, the catalytic domain…
View article: Structural and functional studies of <i>Bacillus subtilis</i> LonBA, member of a newly identified subfamily of Lon proteases
Structural and functional studies of <i>Bacillus subtilis</i> LonBA, member of a newly identified subfamily of Lon proteases Open
ATP-dependent Lon proteases are bifunctional, multidomain, homooligomeric enzymes that play an important role in cellular protein quality control, by being responsible for degradation of abnormal, misfolded, and some regulatory proteins.Th…
View article: Identification of multidentate tyrosyl-DNA phosphodiesterase 1 (TDP1) inhibitors that simultaneously access the DNA, protein and catalytic-binding sites by oxime diversification
Identification of multidentate tyrosyl-DNA phosphodiesterase 1 (TDP1) inhibitors that simultaneously access the DNA, protein and catalytic-binding sites by oxime diversification Open
A click-based oxime protocol to extend small molecule microarray-derived TDP1 inhibitory platform to project into the DNA and TOP1 peptide substrate-binding channels.
View article: Structure of Helicobacter pylori dihydroneopterin aldolase suggests a fragment-based strategy for isozyme-specific inhibitor design
Structure of Helicobacter pylori dihydroneopterin aldolase suggests a fragment-based strategy for isozyme-specific inhibitor design Open
Dihydroneopterin aldolase (DHNA) is essential for folate biosynthesis in microorganisms. Without a counterpart in mammals, DHNA is an attractive target for antimicrobial agents. Helicobacter pylori infection occurs in human stomach of over…
View article: Unique Structural Fold of LonBA Protease from Bacillus subtilis, a Member of a Newly Identified Subfamily of Lon Proteases
Unique Structural Fold of LonBA Protease from Bacillus subtilis, a Member of a Newly Identified Subfamily of Lon Proteases Open
ATP-dependent Lon proteases are key participants in the quality control system that supports the homeostasis of the cellular proteome. Based on their unique structural and biochemical properties, Lon proteases have been assigned in the MER…
View article: Phosphonic acid-containing inhibitors of tyrosyl-DNA phosphodiesterase 1
Phosphonic acid-containing inhibitors of tyrosyl-DNA phosphodiesterase 1 Open
Tyrosyl-DNA phosphodiesterase 1 (TDP1) repairs stalled type I topoisomerase (TOP1)-DNA complexes by hydrolyzing the phosphodiester bond between the TOP1 Y723 residue and the 3′-phosphate of its DNA substrate. Although TDP1 antagonists coul…
View article: Characterization of a broadly specific cadaverine N-hydroxylase involved in desferrioxamine B biosynthesis in Streptomyces sviceus
Characterization of a broadly specific cadaverine N-hydroxylase involved in desferrioxamine B biosynthesis in Streptomyces sviceus Open
N -hydroxylating flavin-dependent monooxygenases (FMOs) are involved in the biosynthesis of hydroxamate siderophores, playing a key role in microbial virulence. Herein, we report the first structural and kinetic characterization of a novel…
View article: Small molecule microarray identifies inhibitors of tyrosyl-DNA phosphodiesterase 1 that simultaneously access the catalytic pocket and two substrate binding sites
Small molecule microarray identifies inhibitors of tyrosyl-DNA phosphodiesterase 1 that simultaneously access the catalytic pocket and two substrate binding sites Open
Using small molecule microarray TDP1 inhibitors have been identified that bind in a trivalent mode.
View article: Structure and activity of PPX/GppA homologs from <i>Escherichia coli</i> and <i>Helicobacter pylori</i>
Structure and activity of PPX/GppA homologs from <i>Escherichia coli</i> and <i>Helicobacter pylori</i> Open
Rapid adaptation to environmental changes is crucial for bacterial survival. Almost all bacteria possess a conserved stringent response system to prompt transcriptional and metabolic responses toward stress. The adaptive process relies on …
View article: Cryo-EM structure of substrate-free E. coli Lon protease provides insights into the dynamics of Lon machinery
Cryo-EM structure of substrate-free E. coli Lon protease provides insights into the dynamics of Lon machinery Open
Energy-dependent Lon proteases play a key role in cellular regulation by degrading short-lived regulatory proteins and misfolded proteins in the cell. The structure of the catalytically inactive S679A mutant of Escherichia coli LonA protea…
View article: Crystallographic study of dihydroneopterin aldolase from <i>Helicobacter pylori</i>
Crystallographic study of dihydroneopterin aldolase from <i>Helicobacter pylori</i> Open
Helicobacter pylori infection can lead to stomach cancer and colorectal cancer.The successful cure of H. pylori has been reduced by drug resistance.The urgency to develop novel antibiotics against H. pylori has fueled continued interest in…
View article: Identification of a ligand binding hot spot and structural motifs replicating aspects of tyrosyl-DNA phosphodiesterase I (TDP1) phosphoryl recognition by crystallographic fragment cocktail screening
Identification of a ligand binding hot spot and structural motifs replicating aspects of tyrosyl-DNA phosphodiesterase I (TDP1) phosphoryl recognition by crystallographic fragment cocktail screening Open
Tyrosyl DNA-phosphodiesterase I (TDP1) repairs type IB topoisomerase (TOP1) cleavage complexes generated by TOP1 inhibitors commonly used as anticancer agents. TDP1 also removes DNA 3′ end blocking lesions generated by chain-terminating nu…
View article: The molecular mechanism of dsRNA processing by a bacterial Dicer
The molecular mechanism of dsRNA processing by a bacterial Dicer Open
Members of the ribonuclease (RNase) III family regulate gene expression by processing dsRNAs. It was previously shown that Escherichia coli (Ec) RNase III recognizes dsRNA with little sequence specificity and the cleavage products are main…
View article: Targeting Protein–Protein Interactions of Tyrosine Phosphatases with Microarrayed Fragment Libraries Displayed on Phosphopeptide Substrate Scaffolds
Targeting Protein–Protein Interactions of Tyrosine Phosphatases with Microarrayed Fragment Libraries Displayed on Phosphopeptide Substrate Scaffolds Open
Chemical library screening approaches that focus exclusively on catalytic events may overlook unique effects of protein-protein interactions that can be exploited for development of specific inhibitors. Phosphotyrosyl (pTyr) residues embed…
View article: Crystal structure of Tdp1 catalytic domain in complex with compound XZ578
Crystal structure of Tdp1 catalytic domain in complex with compound XZ578 Open
Tyrosyl DNA-phosphodiesterase I (TDP1) repairs type IB topoisomerase (TOP1) cleavage complexes generated by TOP1 inhibitors commonly used as anticancer agents. TDP1 also removes DNA 3' end blocking lesions generated by chain-terminating nu…
View article: Binding mode of C/EBPβ and SMAD3 to the p15INK4b promoter
Binding mode of C/EBPβ and SMAD3 to the p15INK4b promoter Open
The basic region:leucine zipper (bZIP) DNA-binding protein, C/EBPβ is a key regulator of numerous cellular processes, but can also contribute to tumorigenesis and to viral diseases.It binds to specific DNA sites as homo-or hetero-dimer and…
View article: Crystal structure of the human dual specificity phosphatase 1 catalytic domain
Crystal structure of the human dual specificity phosphatase 1 catalytic domain Open
The dual specificity phosphatase DUSP1 was the first mitogen activated protein kinase phosphatase (MKP) to be identified. It dephosphorylates conserved tyrosine and threonine residues in the activation loops of mitogen activated protein ki…
View article: Insights Into the Allosteric Inhibition of the SUMO E2 Enzyme Ubc9
Insights Into the Allosteric Inhibition of the SUMO E2 Enzyme Ubc9 Open
Conjugation of the small ubiquitin‐like modifier (SUMO) to protein substrates is an important disease‐associated posttranslational modification, although few inhibitors of this process are known. Herein, we report the discovery of an allos…
View article: Phosphotyrosine Substrate Sequence Motifs for Dual Specificity Phosphatases
Phosphotyrosine Substrate Sequence Motifs for Dual Specificity Phosphatases Open
Protein tyrosine phosphatases dephosphorylate tyrosine residues of proteins, whereas, dual specificity phosphatases (DUSPs) are a subgroup of protein tyrosine phosphatases that dephosphorylate not only Tyr(P) residue, but also the Ser(P) a…
View article: Structure of human dual-specificity phosphatase 7, a potential cancer drug target
Structure of human dual-specificity phosphatase 7, a potential cancer drug target Open
Human dual-specificity phosphatase 7 (DUSP7/Pyst2) is a 320-residue protein that belongs to the mitogen-activated protein kinase phosphatase (MKP) subfamily of dual-specificity phosphatases. Although its precise biological function is stil…
View article: Characterization of the p300 Taz2–p53 TAD2 Complex and Comparison with the p300 Taz2–p53 TAD1 Complex
Characterization of the p300 Taz2–p53 TAD2 Complex and Comparison with the p300 Taz2–p53 TAD1 Complex Open
The p53 tumor suppressor is a critical mediator of the cellular response to stress. The N-terminal transactivation domain of p53 makes protein interactions that promote its function as a transcription factor. Among those cofactors is the h…
View article: Structural analysis of human dual-specificity phosphatase 22 complexed with a phosphotyrosine-like substrate
Structural analysis of human dual-specificity phosphatase 22 complexed with a phosphotyrosine-like substrate Open
4-Nitrophenyl phosphate ( p -nitrophenyl phosphate, pNPP) is widely used as a small molecule phosphotyrosine-like substrate in activity assays for protein tyrosine phosphatases. It is a colorless substrate that upon hydrolysis is converted…