Journal: ACS Central Science

Article Title: Mapping the Azolog Space Enables the Optical Control of New Biological Targets

doi: 10.1021/acscentsci.8b00881

Figure Lengend Snippet: Photophysical evaluation and LTA 4 -hydrolase peptidase assay with LTA 4 H-Photoswitch . (A, B) Enzymatic reactions catalyzed by LTA 4 -hydrolase. (C) The UV–vis spectrum of LTA 4 H-Photoswitch in the dark-adapted (black, trans ), 365 nm adapted (gray, cis ), and 460 nm adapted (blue, trans ) photostationary states. (D) Reversible cycling between isomers with alternating illumination at 365/460 nm. (E) Schematic depiction of l -alanine 4-nitroanilide cleavage by LTA 4 H (PDB: 2VJ8). (F) LTA 4 H peptidase assay with LTA 4 h (1.1 μg) and l -alanine 4-nitroanilide (1 mM) in the presence and absence of cis -LTA 4 H-Photoswitch at different concentrations. Samples were irradiated with 460 nm light after 4 min to yield trans -LTA 4 H-Photoswitch . The slope of 4-nitroaniline absorption (λ = 410 nm) was plotted. (G, H) Representative traces of 4-nitroaniline absorption (λ = 410 nm) before and after application of 460 nm light. Samples were run in triplicates. Error bars represent SEM ** p < 0.01, n.s., not significant, student’s t -test.

Article Snippet: In good agreement with the computational prediction, trans- LTA 4 H-Photoswitch was a more potent inhibitor of LTA 4 H peptidase than the cis -isomer ( Figure ).

Techniques: Irradiation

Journal: ACS Central Science

Article Title: Mapping the Azolog Space Enables the Optical Control of New Biological Targets

doi: 10.1021/acscentsci.8b00881

Figure Lengend Snippet: Synthesis and isomerization of LTA 4 h-Photoswitch . (A) 3D-overlays of parent azologable compounds (gray) with corresponding cis - and trans- azologs (yellow) and 3DAPfp scores of 3D shape similarity comparison. (B) Design of LTA 4 h-Photoswitch based on the azologization of a benzyl phenyl ethers. (C) Chemical synthesis of LTA 4 h-Photoswitch .

Article Snippet: In good agreement with the computational prediction, trans- LTA 4 H-Photoswitch was a more potent inhibitor of LTA 4 H peptidase than the cis -isomer ( Figure ).

Techniques: Comparison

Journal: PLoS ONE

Article Title: Structural Origins for the Loss of Catalytic Activities of Bifunctional Human LTA4H Revealed through Molecular Dynamics Simulations

doi: 10.1371/journal.pone.0041063

Figure Lengend Snippet: The details of all systems subjected to MD simulations.

Article Snippet: Molecular dynamics simulations of LTA4 and tripeptide complex structures with functional mutations were performed to investigate the structural and conformation changes that scripts the observed differences in catalytic functions.

Techniques:

Journal: PLoS ONE

Article Title: Structural Origins for the Loss of Catalytic Activities of Bifunctional Human LTA4H Revealed through Molecular Dynamics Simulations

doi: 10.1371/journal.pone.0041063

Figure Lengend Snippet: (A) LTA4 and (B) RAR selected from the molecular docking studies to be subjected to MD simulations.

Article Snippet: Molecular dynamics simulations of LTA4 and tripeptide complex structures with functional mutations were performed to investigate the structural and conformation changes that scripts the observed differences in catalytic functions.

Techniques:

Journal: PLoS ONE

Article Title: Structural Origins for the Loss of Catalytic Activities of Bifunctional Human LTA4H Revealed through Molecular Dynamics Simulations

doi: 10.1371/journal.pone.0041063

Figure Lengend Snippet: The RMSD, RMSF, and number of intramolecular hydrogen bonds are shown for (A) L-LTA4 (B) L-RAR systems.

Article Snippet: Molecular dynamics simulations of LTA4 and tripeptide complex structures with functional mutations were performed to investigate the structural and conformation changes that scripts the observed differences in catalytic functions.

Techniques:

Journal: PLoS ONE

Article Title: Structural Origins for the Loss of Catalytic Activities of Bifunctional Human LTA4H Revealed through Molecular Dynamics Simulations

doi: 10.1371/journal.pone.0041063

Figure Lengend Snippet: (A) Distance between the metal ion and the epoxy oxygen atom of LTA4. (B) Distance between the metal ion and carbonyl oxygen atom of the N-terminal peptide bond of RAR.

Article Snippet: Molecular dynamics simulations of LTA4 and tripeptide complex structures with functional mutations were performed to investigate the structural and conformation changes that scripts the observed differences in catalytic functions.

Techniques:

Journal: PLoS ONE

Article Title: Structural Origins for the Loss of Catalytic Activities of Bifunctional Human LTA4H Revealed through Molecular Dynamics Simulations

doi: 10.1371/journal.pone.0041063

Figure Lengend Snippet: (A) Number of hydrogen bonds between the protein and LTA4. (B) Number of hydrogen bonds between the protein and RAR.

Article Snippet: Molecular dynamics simulations of LTA4 and tripeptide complex structures with functional mutations were performed to investigate the structural and conformation changes that scripts the observed differences in catalytic functions.

Techniques:

Journal: PLoS ONE

Article Title: Structural Origins for the Loss of Catalytic Activities of Bifunctional Human LTA4H Revealed through Molecular Dynamics Simulations

doi: 10.1371/journal.pone.0041063

Figure Lengend Snippet: The binding mode of LTA4 in (A) WT (grey), (B) E271Q (wheat) (C) R563A (deep teal), and (D) K565A (pink) systems. The amino acid residues and LTA4 are shown in think stick and ball-stick forms, respectively. The metal ion (zinc) present at the active site is shown in sphere form.

Article Snippet: Molecular dynamics simulations of LTA4 and tripeptide complex structures with functional mutations were performed to investigate the structural and conformation changes that scripts the observed differences in catalytic functions.

Techniques: Binding Assay

Journal: PLoS ONE

Article Title: Structural Origins for the Loss of Catalytic Activities of Bifunctional Human LTA4H Revealed through Molecular Dynamics Simulations

doi: 10.1371/journal.pone.0041063

Figure Lengend Snippet: (A) WT and E271Q systems, (B) WT and R563A systems, (C) WT and K565A systems, and (D) all L-LTA4 systems. The WT, E21Q, R563A, and K565A systems are shown in grey, wheat, deep teal, and pink colors, respectively. The amino acid residues and LTA4 are shown in think stick and ball-stick forms, respectively. The metal ion (zinc) present at the active site is shown in sphere form.

Article Snippet: Molecular dynamics simulations of LTA4 and tripeptide complex structures with functional mutations were performed to investigate the structural and conformation changes that scripts the observed differences in catalytic functions.

Techniques:

Journal: PLoS ONE

Article Title: Structural Origins for the Loss of Catalytic Activities of Bifunctional Human LTA4H Revealed through Molecular Dynamics Simulations

doi: 10.1371/journal.pone.0041063

Figure Lengend Snippet: (A) LTA4 and RAR substrates shown in grey and cyan at the active site (B) the catalytic active site residues are shown in thin stick form.

Article Snippet: Molecular dynamics simulations of LTA4 and tripeptide complex structures with functional mutations were performed to investigate the structural and conformation changes that scripts the observed differences in catalytic functions.

Techniques: