A5025128691- Advanced Chemical Physics Studies
- Chemical Reactions and Isotopes
- Protein Structure and Dynamics
- Asymmetric Hydrogenation and Catalysis
- Nuclear Physics and Applications
- Advanced NMR Techniques and Applications
- Signaling Pathways in Disease
- Enzyme Structure and Function
- Mass Spectrometry Techniques and Applications
- Chemical Synthesis and Reactions
- HIV Research and Treatment
- NMR spectroscopy and applications
- Chemical Synthesis and Analysis
- Nuclear reactor physics and engineering
- Peptidase Inhibition and Analysis
- Various Chemistry Research Topics
- Advanced MRI Techniques and Applications
- Spectroscopy and Quantum Chemical Studies
- Bacterial Genetics and Biotechnology
- Catalysis and Oxidation Reactions
- Monoclonal and Polyclonal Antibodies Research
- Catalytic Processes in Materials Science
- Hemoglobin structure and function
- Inorganic and Organometallic Chemistry
- DNA and Nucleic Acid Chemistry
Duke University
2006-2021
Duke Medical Center
1994-2021
Duke University Hospital
1993-2020
International Vaccine Institute
2013
University of Iowa
1999
Environmental Molecular Sciences Laboratory
1999
University of California, San Francisco
1999
Bristol-Myers Squibb (United States)
1996
University of Utah
1972-1995
Resonance Research (United States)
1995
Many human monoclonal antibodies that neutralize multiple clades of HIV-1 are polyreactive and bind avidly to mammalian autoantigens. Indeed, the generation neutralizing 2F5 4E10 epitopes gp41 in man may be proscribed by immune tolerance because mice expressing VH VL regions have a block B cell development is characteristic central tolerance. This developmental blockade implies presence tolerizing autoantigens mimicked membrane-proximal external region gp41. We identify kynureninase (KYNU)...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTEnergy transfer in thermal methyl isocyanide isomerization. Comprehensive investigationSiu C. Chan, Benton S. Rabinovitch, James T. Bryant, Leonard D. Spicer, Fujimoto, Yueh Neu Lin, and P. PavlouCite this: J. Phys. Chem. 1970, 74, 17, 3160–3176Publication Date (Print):August 1, 1970Publication History Published online1 May 2002Published inissue 1 August...
Abstract Calcineurin is important for fungal virulence and a potential antifungal target, but compounds targeting calcineurin, such as FK506, are immunosuppressive. Here we report the crystal structures of calcineurin catalytic (CnA) regulatory (CnB) subunits complexed with FK506 FK506-binding protein (FKBP12) from human pathogens ( Aspergillus fumigatus , Candida albicans Cryptococcus neoformans Coccidioides immitis ). Fungal complexes similar to mammalian complex, comparison FKBP12...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTUse of 1HN-1HN NOEs to Determine Protein Global Folds in Perdeuterated ProteinsRonald A. Venters, William J. Metzler, Leonard D. Spicer, Luciano Mueller, and Bennett T. Farmer IICite this: Am. Chem. Soc. 1995, 117, 37, 9592–9593Publication Date (Print):September 1, 1995Publication History Published online1 May 2002Published inissue 1 September 1995https://pubs.acs.org/doi/10.1021/ja00142a039https://doi.org/10.1021/ja00142a039research-articleACS...
In agreeing to undertake a review with the above title, we did not reckon formidable energy and talent of our immediate predecessor in this area, F. Kaufman, nor coverage offered two companion chapters Volume 20, one on Shock Tube Technique Chemical Kinetics by Belford & Strehlow Isotope Effects Wolfsberg. What appears below then are some vignettes field gas kinetics arbitrarily selected for their interest-to us. We begin discussing effects translational as well internal driving bimolecular...
Abstract A method for deprotection of several N-benzyl derivatives amines to the corresponding amino with ammonium formate and 10% Pd-C is reported.
Significance A major roadblock in the development of an HIV vaccine is need to develop regimens that will induce antibodies bind conserved regions envelope and neutralize many different virus quasispecies. One such target at region closest membrane, glycoprotein (gp) 41 membrane proximal external (MPER). Previous work has demonstrated this both gp41 polypeptide adjacent viral membrane. However, what been missing a view MPER-neutralizing epitopes may look like context trimeric orientation...
Human XPA is an essential component in the multienzyme nucleotide excision repair (NER) pathway. The solution structure of minimal DNA binding domain (XPA-MBD: M98-F219) was recently determined [Buchko et al. (1998) Nucleic Acids Res. 26, 2779−2788, Ikegami Nat. Struct. Biol. 5, 701−706] and shown to consist a compact zinc-binding core loop-rich C-terminal subdomain connected by linker sequence. Here, XPA-MBD further refined using entirely new class restraints based on pseudocontact shifts...
Invasive fungal infections remain difficult to treat and require novel targeting strategies. The 12-kDa FK506-binding protein (FKBP12) is a ubiquitously expressed peptidyl-prolyl isomerase with considerable homology between pathogens thus prime candidate for future efforts generate panfungal strategy. Despite decades of research on FKBPs, their substrates mechanisms action unclear. Here we describe structural, biochemical, in vivo analyses FKBP12s from the pathogenic fungi Candida albicans,...
Uniform double labeling of proteins for NMR studies can be prohibitively expensive, even with an efficient expression and purification scheme, due largely to the high cost [13C6, 99%]glucose. We demonstrate here that uniformly (greater than 95%) 13C 15N double-labeled prepared structure/function by growing cells in defined media containing sodium [1,2-13C2, 99%]acetate as sole carbon source [15N, 99%]ammonium chloride nitrogen source. In addition, we this scheme extended include uniform...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTFT-IR study of nitric oxide chemisorbed on rhodium/aluminaJim Liang, H. P. Wang, and L. D. SpicerCite this: J. Phys. Chem. 1985, 89, 26, 5840–5845Publication Date (Print):December 1, 1985Publication History Published online1 May 2002Published inissue 1 December 1985https://pubs.acs.org/doi/10.1021/j100272a053https://doi.org/10.1021/j100272a053research-articleACS PublicationsRequest reuse permissionsArticle Views228Altmetric-Citations42LEARN ABOUT...
Atomic level characterization of proteins and other macromolecules in the living cell is challenging. Recent advances NMR instrumentation methods, however, have enabled in-cell studies with prospects for multidimensional spectral individual macromolecular components. We present data on behavior MetJ repressor from Escherichia coli , a protein that regulates expression genes involved methionine biosynthesis. whole cells along corresponding lysates vitro preparations pure give clear evidence...
The binding interactions of the methionine repressor protein, MetJ, from Escherichia coli with its cognate, metbox DNA sequence and corepressor S-adenosylmethionine were examined using calorimetric methods. A detailed thermodynamic characterization this system which exhibits recently reported (beta alpha alpha)2 motif provides values for delta G, H, S each step in cycle. These studies show that, presence corepressor, MetJ binds to a single operator site G = -7.7 kcal.mol-1, whereas absence...
High-field, heteronuclear NMR spectroscopy of biological macromolecules in native cellular environments is limited by the low concentrations present and long data acquisition times needed for experiments. Successful 1D 2D have been reported, but 3D experiments conventionally used protein assignment detailed characterization are generally too to maintain cell viability. Here we describe successful vivo implementation a suite fast which generate complete backbone resonances recombinant...
Calcineurin is a critical enzyme in fungal pathogenesis and antifungal drug tolerance and, therefore, an attractive target. Current clinically accessible calcineurin inhibitors, such as FK506, are immunosuppressive to humans, so exploiting inhibition strategy necessitates specificity order avoid inhibiting the human pathway. Harnessing calcineurin-inhibitor crystal structures, we recently developed less FK506 analog, APX879, with broad-spectrum activity demonstrable efficacy murine model of...
Whole-genome sequencing of bacteria has proceeded at an exponential pace but annotation validation lagged behind. For instance, the MetJ regulon, which controls methionine biosynthesis and transport, been studied almost exclusively in E. coli Salmonella, homologs exist a variety other species. These include some that are pathogenic (e.g. Yersinia) important for environmental remediation Shewanella) many have not extensively characterized literature. We determined likely composition regulon...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTEnergy transfer in thermal methyl isocyanide isomerization. Relative cross sections of fluoroalkanes and nitrilesSiu C. Chan, James T. Bryant, L. D. Spicer, Benton S. RabinovitchCite this: J. Phys. Chem. 1970, 74, 10, 2058–2064Publication Date (Print):May 1, 1970Publication History Published online1 May 2002Published inissue 1 1970https://pubs.acs.org/doi/10.1021/j100909a003https://doi.org/10.1021/j100909a003research-articleACS PublicationsRequest...