Search Results - "Sigala, Paul A"
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The interdependence of isoprenoid synthesis and apicoplast biogenesis in malaria parasites
Published in PLoS pathogens (26-10-2023)“…Isoprenoid precursor synthesis is an ancient and fundamental function of plastid organelles and a critical metabolic activity of the apicoplast in Plasmodium…”
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The peculiarities and paradoxes of Plasmodium heme metabolism
Published in Annual review of microbiology (01-01-2014)“…For over a century, heme metabolism has been recognized to play a central role during intraerythrocytic infection by Plasmodium parasites, the causative agent…”
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Doxycycline has distinct apicoplast-specific mechanisms of antimalarial activity
Published in eLife (02-11-2020)“…Doxycycline (DOX) is a key antimalarial drug thought to kill parasites by blocking protein translation in the essential apicoplast organelle. Clinical use is…”
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4
Plasmodium heme biosynthesis: To be or not to be essential?
Published in PLoS pathogens (01-09-2017)“…About the Authors: Daniel E. Goldberg * E-mail: dgoldberg@wustl.edu (DEG); p.sigala@utah.edu (PAS) Affiliation: Departments of Medicine and Molecular…”
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Direct tests of cytochrome c and c1 functions in the electron transport chain of malaria parasites
Published in Proceedings of the National Academy of Sciences - PNAS (09-05-2023)“…The mitochondrial electron transport chain (ETC) of Plasmodium malaria parasites is a major antimalarial drug target, but critical cytochrome (cyt) functions…”
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Determination of Hydrogen Bond Structure in Water versus Aprotic Environments To Test the Relationship Between Length and Stability
Published in Journal of the American Chemical Society (06-05-2015)“…Hydrogen bonds profoundly influence the architecture and activity of biological macromolecules. Deep appreciation of hydrogen bond contributions to…”
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Critical role for isoprenoids in apicoplast biogenesis by malaria parasites
Published in eLife (08-03-2022)“…Isopentenyl pyrophosphate (IPP) is an essential metabolic output of the apicoplast organelle in malaria parasites and is required for prenylation-dependent…”
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Quantitative, directional measurement of electric field heterogeneity in the active site of ketosteroid isomerase
Published in Proceedings of the National Academy of Sciences - PNAS (07-02-2012)“…Understanding the electrostatic forces and features within highly heterogeneous, anisotropic, and chemically complex enzyme active sites and their connection…”
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Direct Tests of Enzymatic Heme Degradation by the Malaria Parasite Plasmodium falciparum
Published in The Journal of biological chemistry (02-11-2012)“…Malaria parasites generate vast quantities of heme during blood stage infection via hemoglobin digestion and limited de novo biosynthesis, but it remains…”
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10
Hydrogen bond dynamics in the active site of photoactive yellow protein
Published in Proceedings of the National Academy of Sciences - PNAS (09-06-2009)“…Hydrogen bonds play major roles in biological structure and function. Nonetheless, hydrogen-bonded protons are not typically observed by X-ray crystallography,…”
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Divergent acyl carrier protein decouples mitochondrial Fe-S cluster biogenesis from fatty acid synthesis in malaria parasites
Published in eLife (06-10-2021)“…Most eukaryotic cells retain a mitochondrial fatty acid synthesis (FASII) pathway whose acyl carrier protein (mACP) and 4-phosphopantetheine (Ppant) prosthetic…”
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12
Deconvoluting heme biosynthesis to target blood-stage malaria parasites
Published in eLife (14-07-2015)“…Heme metabolism is central to blood-stage infection by the malaria parasite Plasmodium falciparum. Parasites retain a heme biosynthesis pathway but do not…”
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13
Multiple-Streams Focusing-Based Cell Separation in High Viscoelasticity Flow
Published in ACS omega (15-11-2022)“…Viscoelastic flow has been widely used in microfluidic particle separation processes, in which particles get focused on the channel center in diluted…”
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14
Dissecting the paradoxical effects of hydrogen bond mutations in the ketosteroid isomerase oxyanion hole
Published in Proceedings of the National Academy of Sciences - PNAS (02-02-2010)“…The catalytic importance of enzyme active-site interactions is frequently assessed by mutating specific residues and measuring the resulting rate reductions…”
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15
Testing Geometrical Discrimination within an Enzyme Active Site: Constrained Hydrogen Bonding in the Ketosteroid Isomerase Oxyanion Hole
Published in Journal of the American Chemical Society (15-10-2008)“…Enzymes are classically proposed to accelerate reactions by binding substrates within active-site environments that are structurally preorganized to optimize…”
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Quantitative dissection of hydrogen bond-mediated proton transfer in the ketosteroid isomerase active site
Published in Proceedings of the National Academy of Sciences - PNAS (09-07-2013)“…Hydrogen bond networks are key elements of protein structure and function but have been challenging to study within the complex protein environment. We have…”
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Do Ligand Binding and Solvent Exclusion Alter the Electrostatic Character within the Oxyanion Hole of an Enzymatic Active Site?
Published in Journal of the American Chemical Society (10-10-2007)“…We report the site-specific incorporation of a thiocyanate vibrational probe into the active-site oxyanion hole of ketosteroid isomerase (KSI) to test the…”
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In-Cell Enzymology To Probe His–Heme Ligation in Heme Oxygenase Catalysis
Published in Biochemistry (Easton) (30-08-2016)“…Heme oxygenase (HO) is a ubiquitous enzyme with key roles in inflammation, cell signaling, heme disposal, and iron acquisition. HO catalyzes the oxidative…”
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Testing electrostatic complementarity in enzyme catalysis: hydrogen bonding in the ketosteroid isomerase oxyanion hole
Published in PLoS biology (01-04-2006)“…A longstanding proposal in enzymology is that enzymes are electrostatically and geometrically complementary to the transition states of the reactions they…”
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Identification of a divalent metal transporter required for cellular iron metabolism in malaria parasites
Published in Proceedings of the National Academy of Sciences - PNAS (05-11-2024)“…malaria parasites invade and multiply inside red blood cells (RBCs), the most iron-rich compartment in humans. Like all cells, requires nutritional iron to…”
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