A5054562365- Lysosomal Storage Disorders Research
- Protein Kinase Regulation and GTPase Signaling
- Trypanosoma species research and implications
- Particle physics theoretical and experimental studies
- Quantum Chromodynamics and Particle Interactions
- Cellular transport and secretion
- Neonatal Health and Biochemistry
- High-Energy Particle Collisions Research
- Metabolism and Genetic Disorders
- Research on Leishmaniasis Studies
- Venomous Animal Envenomation and Studies
- Biochemical and Molecular Research
- Carbohydrate Chemistry and Synthesis
- Biomedical Research and Pathophysiology
- Lipid Membrane Structure and Behavior
- Chemical Synthesis and Analysis
- Receptor Mechanisms and Signaling
- Synthesis and Biological Evaluation
- Cytomegalovirus and herpesvirus research
- Erythrocyte Function and Pathophysiology
- HIV/AIDS drug development and treatment
- Malaria Research and Control
- Asthma and respiratory diseases
- Mass Spectrometry Techniques and Applications
- Ubiquitin and proteasome pathways
University of Washington
2015-2024
University of California, San Francisco
1998-2023
Seattle University
1999-2023
Duke University
2019-2023
Children's Hospital of Eastern Ontario
2023
University of Ottawa
2023
Ottawa Hospital
2023
UCSF Benioff Children's Hospital
2023
Karlsruhe Institute of Technology
2017-2022
Beihang University
2019
The Diels-Alder reaction is a cornerstone in organic synthesis, forming two carbon-carbon bonds and up to four new stereogenic centers one step. No naturally occurring enzymes have been shown catalyze bimolecular reactions. We describe the de novo computational design experimental characterization of catalyzing with high stereoselectivity substrate specificity. X-ray crystallography confirms that structure matches for most active enzymes, binding site substitutions reprogram Designed...
A chemical description of the action phospholipase A2 (PLA2) can now be inferred with confidence from three high-resolution x-ray crystal structures. The first is structure PLA2 venom Chinese cobra (Naja naja atra) in a complex phosphonate transition-state analogue. This enzyme typical large, well-studied homologous family PLA2S. second similar evolutionarily distant bee-venom PLA2. third uninhibited venom. Despite different molecular architectures and PLA2s, analogue interacts nearly...
The crystal structure of a complex between phosphonate transition-state analogue and the phospholipase A2 (PLA2) from Naja naja atra venom has been solved refined to resolution 2.0 angstroms. identical stereochemistry two complexes that comprise crystal's asymmetric unit indicates both manner in which transition state is stabilized how hydrophobic fatty acyl chains substrate are accommodated by enzyme during interfacial catalysis. critical features suggest chemistry binding catalysis same as...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSlow- and tight-binding inhibitors of the 85-kDa human phospholipase A2Ian P. Street, Hung Kuei Lin, France Laliberte, Farideh Ghomashchi, Zhaoyin Wang, Helene Perrier, Nathalie M. Tremblay, Zheng Huang, Philip K. Weech, Michael H. GelbCite this: Biochemistry 1993, 32, 23, 5935–5940Publication Date (Print):June 15, 1993Publication History Published online1 May 2002Published inissue 15 June...
We describe a computationally designed enzyme, formolase (FLS), which catalyzes the carboligation of three one-carbon formaldehyde molecules into one three-carbon dihydroxyacetone molecule. The existence FLS enables design new carbon fixation pathway, consisting small number thermodynamically favorable chemical transformations that convert formate sugar in central metabolism. pathway is predicted to use more efficiently and with less backward flux than any naturally occurring assimilation...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTFluoro ketone inhibitors of hydrolytic enzymesMichael H. Gelb, John P. Svaren, and Robert AbelesCite this: Biochemistry 1985, 24, 8, 1813–1817Publication Date (Print):April 9, 1985Publication History Published online1 May 2002Published inissue 9 April 1985https://pubs.acs.org/doi/10.1021/bi00329a001https://doi.org/10.1021/bi00329a001research-articleACS PublicationsRequest reuse permissionsArticle Views999Altmetric-Citations299LEARN ABOUT THESE...
With the full data sample of $772 \times 10^6$ $B{\bar B}$ pairs recorded by Belle detector at KEKB electron-positron collider, decay $\bar{B} \rightarrow D^* \tau^- \bar{\nu}_\tau$ is studied with hadronic $\tau$ decays $\tau^- \pi^- \nu_\tau$ and \rho^- \nu_\tau$. The polarization $P_\tau(D^*)$ in two-body measured, as well ratio branching fractions $R(D^{*}) = \mathcal{B}(\bar {B} \bar{\nu}_\tau) / \mathcal{B}(\bar{B} \ell^- \bar{\nu}_\ell)$, where $\ell^-$ denotes an electron or a muon....
Significance On activation, blood platelets package components from their cytoplasm into microparticles (MPs), tiny vesicles released by cytoplasmic membrane budding and shedding. Given that MPs can impact other cellular lineages on internalization, we aimed to decipher the mechanisms promoting MP internalization recipients. We modeled neutrophils identified a predominant lipid, 12(S)-hydroxyeicosatetranoic acid, as mediator critical for promotion of internalization. were found inside...
Expression of the full set human and mouse groups I, II, V, X, XII secreted phospholipases A(2) (sPLA(2)s) in Escherichia coli insect cells has provided pure recombinant enzymes for detailed comparative interfacial kinetic binding studies. The mammalian sPLA(2)s display dramatically different sensitivity to dithiothreitol. specific activity hydrolysis vesicles differing phospholipid composition by these varies up 4 orders magnitude, yet all similar catalytic site specificity toward...
The rat mast cell line RBL-2H3.1 contains an 85-kDa cytosolic phospholipase A2 (cPLA2) that is very likely involved in liberating arachidonate from membrane phospholipid for the synthesis of eicosanoids following stimulation with either calcium ionophore or IgE/antigen. In this study, intracellular location cPLA2 was determined using immunofluorescence microscopy and immuno-gold electron microscopy. nonstimulated cells, distributed throughout cytosol excluded nucleoplasm. Following...
Newborn screening for deficiency in the lysosomal enzymes that cause Fabry, Gaucher, Krabbe, Niemann-Pick A/B, and Pompe diseases is warranted because treatment these syndromes now available or anticipated near feature. We describe a multiplex method all five uses newborn-screening cards containing dried blood spots as enzyme source.We used cassette of substrates internal standards to directly quantify enzymatic activities, tandem mass spectrometry product detection. Rehydrated were...
We recently showed that HeLa cell lamin B is modified by a mevalonic acid derivative. Here we identified the amino acid, determined its mode of linkage to derivative, and established derivative's structure. A cysteine residue because experiments with had been biosynthetically labeled [3H]mevalonic or [35S]cysteine then extensively digested proteases yielded 3H- 35S-labeled products co-chromatographed in five successive systems. thioether rather than thioester involved derivative could be...
Hutchinson–Gilford progeria syndrome (HGPS), a progeroid in children, is caused by mutations LMNA (the gene for prelamin A and lamin C) that result the deletion of 50 aa within A. In normal cells, “ CAAX protein” farnesylated then processed further to generate mature A, which structural protein nuclear lamina. The mutant HGPS, commonly called progerin, retains motif triggers farnesylation, but 50-aa prevents subsequent processing presence progerin adversely affects integrity lamina,...
Defects in the biogenesis of lamin A from its farnesylated precursor, prelamin A, lead to accumulation at nuclear envelope, cause misshapen nuclei, and result progeroid syndromes. deficiency ZMPSTE24, a protease involved processing, leads accumulation, an absence mature lethal perinatal syndrome: restrictive dermopathy (RD). Hutchinson-Gilford progeria syndrome (HGPS) is caused by mutant that cannot be processed A. The hallmark cellular abnormality RD HGPS nuclei. We hypothesized...
Phospholipase A2 (PLA2) participates in a wide range of cellular processes including inflammation and transmembrane signaling. A human nonpancreatic secretory PLA2 (hnps-PLA2) has been identified that is found high concentrations the synovial fluid patients with rheumatoid arthritis plasma septic shock. This enzyme secreted from certain cell types response to proinflammatory cytokines, tumor necrosis factor or interleukin-1. The crystal structures calcium-bound form this have determined at...
Group IIA secreted phospholipase A(2) (sPLA2) is known to display potent Gram-positive bactericidal activity in vitro and vivo. We have analyzed the of full set recombinant murine human groups I, II, V, X, XII sPLA2s on Listeria monocytogenes, Staphylococcus aureus, Escherichia coli. The rank order potency among against bacteria group > X V IIE IB, IIF (for sPLA2s: IID IIC, IIF), only displays detectable Gram-negative bacterium E. These studies show that highly basic with exception ability...
The signaling enzyme phospholipase D (PLD) and the lipid second messenger it generates, phosphatidic acid (PA), are implicated in many cell biological processes, including Ras activation, spreading, stress fiber formation, chemotaxis, membrane vesicle trafficking. PLD production of PA is inhibited by primary alcohol 1-butanol, which has thus been widely employed to identify PLD/PA-driven processes. However, 1-butanol does not always effectively reduce accumulation, its use may result...
The crystal structure of a complex between phosphonate transition-state analogue and the phospholipase A 2 (PLA ) from Naja naja atra venom has been solved refined to resolution 2.0 angstroms. identical stereochemistry two complexes that comprise crystal's asymmetric unit indicates both manner in which transition state is stabilized how hydrophobic fatty acyl chains substrate are accommodated by enzyme during interfacial catalysis. critical features suggest chemistry binding catalysis same...