Journal of Biological Chemistry
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- Aacr, CSA, American Society for Biochemistry and Molecular Biology, Ama, Nephrology, Endocrine, Aaas, Rupress, Highwire, Csh, and Proquest
Crystal Structure of Anti-polysialic Acid Antibody Single Chain Fv Fragment Complexed with Octasialic Acid: INSIGHT INTO THE BINDING PREFERE...
We report the crystal structure of mAb735 single chain variable fragment (scFv735) in complex with octasialic acid at 1.8 Å resolution. In the asymmetric unit, two scFv735 molecules associate with one octasialic acid. In both complexes of the unit, all the complementarity-determining regions except...
Insulin Secretion and Ca2+ Dynamics in β-Cells Are Regulated by PERK (EIF2AK3) in Concert with Calcineurin.
We used a newly developed and highly specific inhibitor of PERK to determine the immediate effects of acute ablation of PERK activity. We found that inhibition of PERK in human and rodent β-cells causes a rapid inhibition of secretagogue-stimulated subcellular Ca(2+) signaling and insulin secretion....
Sirtuin 3 (SIRT3) Protein Regulates Long-chain Acyl-CoA Dehydrogenase by Deacetylating Conserved Lysines Near the Active Site.
We previously demonstrated increased LCAD lysine acetylation in SIRT3 knockout mice concomitant with reduced LCAD activity and reduced fatty acid oxidation. To study the effects of acetylation on LCAD and determine sirtuin 3 (SIRT3) target sites, we chemically acetylated recombinant LCAD. Acetylatio...
A Knock-in Mouse Model of Human PHD2 Gene-associated Erythrocytosis Establishes a Haploinsufficiency Mechanism.
We generated and characterized a mouse line in which a P294R knock-in mutation has been introduced into the mouse Phd2 locus to model the first reported human PHD2 mutation (P317R). Phd2(P294R/+) mice display a degree of erythrocytosis equivalent to that seen in Phd2(+/-) mice. The Phd2(P294R/+)-ass...
Herpesvirus-associated Ubiquitin-specific Protease (HAUSP) Modulates Peroxisome Proliferator-activated Receptor γ (PPARγ) Stability through ...
Our results demonstrate that the stability and activity of PPARγ are modulated by the deubiquitinating activity of HAUSP, which may be a target for the development of anti-diabetic drugs....
A Key Role for Plasmodium Subtilisin-like SUB1 Protease in Egress of Malaria Parasites from Host Hepatocytes.
We show that SUB1 plays an essential role at the hepatic stage. Stage-specific sub1 invalidation during prehepatocytic development showed that SUB1-deficient parasites failed to rupture the parasitophorous vacuole membrane and to egress from hepatocytes. Furthermore, mechanically released parasites...
Inositol 1,4,5-Trisphosphate (IP3) Receptor Up-regulation in Hypertension Is Associated with Sensitization of Ca2+ Release and Vascular Smoo...
We compared IP3R expression and function between mesenteric arteries of normotensive and hypertensive animals. Levels of IP3R transcript and protein were significantly increased in mesenteric arteries of hypertensive animals, and pharmacological inhibition of the IP3R revealed a higher contribution...
Regulation of the Src-PP2A Interaction in Tumor Necrosis Factor (TNF)-related Apoptosis-inducing Ligand (TRAIL)-induced Apoptosis.
We show that the regulation of the PP2A and Src interaction plays a critical role in TRAIL resistance. Specifically, we show that TRAIL treatment activates the tyrosine kinase Src, which subsequently phosphorylates caspase-8 at tyrosine 380, leading to the inhibition of caspase-8 activation. We also...
Tyrosyl Radicals in Dehaloperoxidase: HOW NATURE DEALS WITH EVOLVING AN OXYGEN-BINDING GLOBIN TO A BIOLOGICALLY RELEVANT PEROXIDASE.
I in several tyrosine mutants was obtained. Variants that formed Compound I showed an increase in the catalytic rate for substrate oxidation but also an increase in heme bleaching, suggesting that the tyrosines are necessary for protecting the enzyme from oxidizing itself. This protective role of ty...
Using mutagenesis and structural biology to map the binding site for the Plasmodium falciparum merozoite protein PfRh4 on the human immune a...
We have employed ELISA, co-immunoprecipitation and surface plasmon resonance to demonstrate that CCP 1 contains all the critical residues for PfRh4 interaction. We fine mapped by homologous substitution mutagenesis the PfRh4-binding site on CCP 1 and visualized it with a solution structure of CCPs 1...