Johnsson, Kai, Schultz, Peter G.
The enzymic oxidn. of isoniazid by the catalase-peroxidase of Mycobacterium tuberculosi was studied. The reaction products suggest two reaction pathways involving both electrophilic and radical...
Johnsson, Kai, King, David S., Schultz, Peter G.
The inactivation of the enoyl-reductase InhA from Mycobacterium tuberculosis by reactive intermediates formed during the oxidn. of isoniazid and ethionamide was studied. Both drugs can generate...
Organization of 'nanocrystal molecules' using DNA (2006)
Alivisatos, A. Paul, Johnsson, Kai P., Peng, Xiaogang, Wilson, Troy E., Loweth, Colin J., Schultz, Peter G.
The authors describe a strategy for the synthesis of 'nanocrystal mols.', in which discrete nos. of Au nanocrystals are organized into spatially defined structures based on Watson-Crick base-pairing...
Johnsson, Kai, Froland, Wayne A., Schultz, Peter G.
Wild-type catalase-peroxidase KatG from Mycobacterium tuberculosis as well as a specific mutant (R463L) frequently found in isoniazid-resistant strains have been overexpressed in Escherichia coli,...
Damoiseaux, Robert, Schultz, Peter G., Johnsson, Kai
A stepwise approach to the development of artificial O6-alkylguanine-DNA alkyltransferases (AGTs) and its application to the in vitro selection of antibodies with highly reactive cysteine residues...
Optimization of Xenon Biosensors for Detection of Protein Interactions (2005)
Lowery, Thomas J., Garcia, Sandra, Chavez, Lana, Ruiz, E. Janette, Wu, Tom, Brotin, Thierry, ...
Hyperpolarized 129Xe NMR can detect the presence of specific low-concentration biomolecular analytes by means of the xenon biosensor, which consists of a water-soluble, targeted cryptophane-A cage...
NOTE: Text or symbols not renderable in plain ASCII are indicated by [...]. Abstract is included in .pdf document. CHAPTER I Direct studies of the ground and excited state properties of kinetically...
Development of a functionalized Xenon biosensor (2004)
Spence, Megan M., Ruiz, E. Janette, Rubin, Seth M., Lowery, Thomas J., Winssinger, Nicolas, Schultz, Peter G., ...
NMR-based biosensors that utilize laser-polarized xenon offer potential advantages beyond current sensing technologies. These advantages include the capacity to simultaneously detect multiple...
In Vivo Incorporation of Unnatural Amino Acids into Proteins (1998)
A new orthogonal suppressor tRNA was derived from tRNA2 to the G1n, which is not a substrate for any E. coil aminoacyl-tRNA synthetase, yet functions with the E. co/i translational machinery....
In Vivo Incorporation of Unnatural Amino Acids into Proteins (1998)
A method for the site-specific incorporation of unnatural amino acids into proteins in vivo would significantly facilitate studies of the cellular function of proteins, as well as make possible the...
Antibody catalysis of peptidyl-prolyl cis-trans isomerization in the folding of RNase T1 (1998)
Ma, Lifu, Hsieh-Wilson, Linda C., Schultz, Peter G.
An antibody generated to an alpha-keto amide containing hapten 1 catalyzes the cis-trans isomerization of peptidyl-prolyl amide bonds in peptides and in the protein RNase T1. The antibody-catalyzed...
Exploiting Chemical Libraries, Structure, and Genomics in the Search for Kinase Inhibitors (1998)
Kim, Sung-Hou, Meijer, Laurent, LeClerc, Sophie, Barnes, Georjana, Morgan, David O., Espinoza, F. Hernan, ...
Selective protein kinase inhibitors were developed on the basis of the unexpected binding mode of 2,6,9-trisubstituted purines to the adenosine triphosphate-binding site of the human cyclin-dependent...
Exploiting Chemical Libraries, Structure, and Genomics in the Search for Kinase Inhibitors (1998)
Lockhart, David J., Kim, Sung-Hou, Meijer, Laurent, LeClerc, Sophie, Barnes, Georjana, Morgan, David O., ...
Selective protein kinase inhibitors were developed on the basis of the unexpected binding mode of 2,6,9-trisubstituted purines to the adenosine triphosphate-binding site of the human cyclin-dependent...
Novel Biopolymeric Materials. (1997)
Efficient synthetic methods have been generated for the (i) synthesis of libraries of unnatural oligomers, (ii) methods have been developed for the generation and screening of libraries of...
Insights into antibody catalysis: Structure of an oxygenation catalyst at 1.9-Å resolution (1996)
Hsieh-Wilson, Linda C., Schultz, Peter G., Stevens, Raymond C.
The x-ray crystal structures of the sulfide oxidase antibody 28B4 and of antibody 28B4 complexed with hapten have been solved at 2.2-Å and 1.9-Å resolution, respectively. To our knowledge, these...
Schultz, Peter G., Dervan, Peter B.
In the presence of O2 and 5 mM dithiothreitol, penta-N-methylpyrrolecarboxamide-EDTA·Fe(II) [P5E·Fe(II)] at 0.5 µ M cleaves pBR322 plasmid DNA (50 µ M in base pairs) on opposite strands to afford...
NOTE: Text or symbols not renderable in plain ASCII are indicated by [...]. Abstract is included in .pdf document. CHAPTER I Direct studies of the ground and excited state properties of kinetically...
Single-molecule fluorescence spectroscopy of enzyme conformational dynamics and cleavage mechanism
Ha, Taekjip, Ting, Alice Y., Liang, Joy, Caldwell, W. Brett, Deniz, Ashok A., Chemla, Daniel S., ...
Fluorescence resonance energy transfer and fluorescence polarization anisotropy are used to investigate single molecules of the enzyme staphylococcal nuclease. Intramolecular fluorescence resonance...
Misregulation of gene expression in primary fibroblasts lacking poly(ADP-ribose) polymerase
Simbulan-Rosenthal, Cynthia M., Ly, Danith H., Rosenthal, Dean S., Konopka, Genevieve, Luo, RuiBai, Wang, Zhao-Qi, ...
Poly(ADP-ribose) polymerase (PARP) is implicated in the maintenance of genomic integrity, given that inhibition or depletion of this enzyme increases genomic instability in cells exposed to genotoxic...
Effects of environmental enrichment on gene expression in the brain
Rampon, Claire, Jiang, Cecilia H., Dong, Helin, Tang, Ya-Ping, Lockhart, David J., Schultz, Peter G., ...
An enriched environment is known to promote structural changes in the brain and to enhance learning and memory performance in rodents [Hebb, D. O. (1947) Am. Psychol. 2, 306–307]. To better...
Yu, Jaehoon, Choi, So Young, Moon, Kyung-Duk, Chung, Hyun-Ho, Youn, Hyun Joo, Jeong, Sunjoo, ...
Antibodies were generated against the positively charged chair-like glycosidase inhibitor nojirimycin by in vitro immunization. A number of catalytic antibodies were isolated, one of which catalyzes...
Progress toward the evolution of an organism with an expanded genetic code
Liu, David R., Schultz, Peter G.
Several significant steps have been completed toward a general method for the site-specific incorporation of unnatural amino acids into proteins in vivo. An “orthogonal” suppressor tRNA was...
Rosania, Gustavo R., Merlie, John, Gray, Nathanael, Chang, Young-Tae, Schultz, Peter G., Heald, Rebecca
Cellular differentiation is a complex process involving growth arrest, exit from the cell cycle, and expression of differentiated cell-type-specific functions. To identify small molecules promoting...
SDS capillary gel electrophoresis of proteins in microfabricated channels
Yao, Shao, Anex, Deon S., Caldwell, W. Brett, Arnold, Don W., Smith, Katherine B., Schultz, Peter G.
Analysis of variations in the concentrations or structures of biomolecules (e.g., mRNAs, proteins, peptides, natural products) that occur either naturally or in response to environmental or genetic...
Kanamori, Takashi, Nishikawa, Shuh-ichi, Nakai, Masato, Shin, Injae, Schultz, Peter G., Endo, Toshiya
Translocation of mitochondrial precursor proteins across the mitochondrial outer membrane is facilitated by the translocase of the outer membrane (TOM) complex. By using site-specific...
Deniz, Ashok A., Dahan, Maxime, Grunwell, Jocelyn R., Ha, Taekjip, Faulhaber, Ann E., Chemla, Daniel S., ...
Photon bursts from single diffusing donor-acceptor labeled macromolecules were used to measure intramolecular distances and identify subpopulations of freely diffusing macromolecules in a...
Antibody catalysis of peptidyl-prolyl cis-trans isomerization in the folding of RNase T1
Ma, Lifu, Hsieh-Wilson, Linda C., Schultz, Peter G.
An antibody generated to an α-keto amide containing hapten 1 catalyzes the cis-trans isomerization of peptidyl-prolyl amide bonds in peptides and in the protein RNase T1. The antibody-catalyzed...
Liu, David R., Magliery, Thomas J., Pastrnak, Miro, Schultz, Peter G.
In an effort to expand the scope of protein mutagenesis, we have completed the first steps toward a general method to allow the site-specific incorporation of unnatural amino acids into proteins in...
Deniz, Ashok A., Laurence, Ted A., Beligere, Gangamani S., Dahan, Maxime, Martin, Andrew B., Chemla, Daniel S., ...
We report single-molecule folding studies of a small, single-domain protein, chymotrypsin inhibitor 2 (CI2). CI2 is an excellent model system for protein folding studies and has been extensively...
A method for directed evolution and functional cloning of enzymes
Pedersen, Henrik, Hölder, Swen, Sutherlin, Daniel P., Schwitter, Urs, King, David S., Schultz, Peter G.
A general scheme is described for the in vitro evolution of protein catalysts in a biologically amplifiable system. Substrate is covalently and site specifically attached by a flexible tether to the...
The effects of aging on gene expression in the hypothalamus and cortex of mice
Jiang, Cecilia H., Tsien, Joe Z., Schultz, Peter G., Hu, Yinghe
A better understanding of the molecular effects of aging in the brain may help to reveal important aspects of organismal aging, as well as processes that lead to age-related brain dysfunction. In...
The in vivo neuromodulatory effects of the herbal medicine ginkgo biloba
Watanabe, Coran M. H., Wolffram, Siegfried, Ader, Peter, Rimbach, Gerald, Packer, Lester, Maguire, John J., ...
Extracts of Ginkgo biloba leaves are consumed as dietary supplements to counteract chronic, age-related neurological disorders. We have applied high-density oligonucleotide microarrays to define the...
Functionalized xenon as a biosensor
Spence, Megan M., Rubin, Seth M., Dimitrov, Ivan E., Ruiz, E. Janette, Wemmer, David E., Pines, Alexander, ...
The detection of biological molecules and their interactions is a significant component of modern biomedical research. In current biosensor technologies, simultaneous detection is limited to a small...
Block-Alper, Laura, Webster, Paul, Zhou, Xianghong, Supeková, Lubica, Wong, Wing Hung, Schultz, Peter G., ...
Expression of the 180-kDa canine ribosome receptor in Saccharomyces cerevisiae leads to the accumulation of ER-like membranes. Gene expression patterns in strains expressing various forms of p180,...
Universal bases for hybridization, replication and chain termination
Berger, Markus, Wu, Yiqin, Ogawa, Anthony K., McMinn, Dustin L., Schultz, Peter G., Romesberg, Floyd E.
Several unnatural, predominantly hydrophobic nucleobases that pack efficiently in duplex DNA without hydrogen bonding functionalities are reported to circumvent the hydrogen bonding-based...
Addition of a photocrosslinking amino acid to the genetic code of Escherichia coli
Chin, Jason W., Martin, Andrew B., King, David S., Wang, Lei, Schultz, Peter G.
Benzophenones are among the most useful photocrosslinking agents in biology. We have evolved an orthogonal aminoacyl-tRNA synthetase/tRNA pair that makes possible the in vivo incorporation of...
Profiling protein function with small molecule microarrays
Winssinger, Nicolas, Ficarro, Scott, Schultz, Peter G., Harris, Jennifer L.
The regulation of protein function through posttranslational modification, local environment, and protein–protein interaction is critical to cellular function. The ability to analyze on a...
Gene expression during the priming phase of liver regeneration after partial hepatectomy in mice
Su, Andrew I., Guidotti, Luca G., Pezacki, John Paul, Chisari, Francis V., Schultz, Peter G.
Understanding the gene-expression patterns during liver regeneration may help to reveal how regenerative processes are initiated and controlled as well as shed new light onto processes that lead to...
Directed evolution of the site specificity of Cre recombinase
Santoro, Stephen W., Schultz, Peter G.
Cre recombinase from bacteriophage P1 recognizes a 34-bp recombination site, loxP, with exquisite sequence specificity and catalyzes the site-specific insertion, excision, or rearrangement of DNA. To...
Large-scale analysis of the human and mouse transcriptomes
Su, Andrew I., Cooke, Michael P., Ching, Keith A., Hakak, Yaron, Walker, John R., Wiltshire, Tim, ...
High-throughput gene expression profiling has become an important tool for investigating transcriptional activity in a variety of biological samples. To date, the vast majority of these experiments...
Xia, Gang, Chen, Liangjing, Sera, Takashi, Fa, Ming, Schultz, Peter G., Romesberg, Floyd E.
The creation of novel enzymatic function is of great interest, but remains a challenge because of the large sequence space of proteins. We have developed an activity-based selection method to evolve...
Lesley, Scott A., Kuhn, Peter, Godzik, Adam, Deacon, Ashley M., Mathews, Irimpan, Kreusch, Andreas, ...
Structural genomics is emerging as a principal approach to define protein structure–function relationships. To apply this approach on a genomic scale, novel methods and technologies must be...
Genomic analysis of the host response to hepatitis C virus infection
Su, Andrew I., Pezacki, John P., Wodicka, Lisa, Brideau, Amy D., Supekova, Lubica, Thimme, Robert, ...
We have examined the progression of hepatitis C virus (HCV) infections by gene expression analysis of liver biopsies in acutely infected chimpanzees that developed persistent infection, transient...
Wieland, Stefan F., Vega, Raquel G., Müller, Rolf, Evans, Claire F., Hilbush, Brian, Guidotti, Luca G., ...
We have previously shown that alpha/beta interferon (IFN-α/β) and IFN-γ inhibit hepatitis B virus (HBV) replication noncytopathically in the livers of HBV transgenic mice and in hepatocyte cell...
Addition of the keto functional group to the genetic code of Escherichia coli
Wang, Lei, Zhang, Zhiwen, Brock, Ansgar, Schultz, Peter G.
Although the keto group is the most versatile of the functional groups in organic chemistry, it is absent in the genetically encoded amino acids. To overcome this natural limitation on protein...
Profiling of tyrosine phosphorylation pathways in human cells using mass spectrometry
Salomon, Arthur R., Ficarro, Scott B., Brill, Laurence M., Brinker, Achim, Phung, Qui T., Ericson, Christer, ...
The reversible phosphorylation of tyrosine residues is an important mechanism for modulating biological processes such as cellular signaling, differentiation, and growth, and if deregulated, can...
Synthetic small molecules that control stem cell fate
Ding, Sheng, Wu, Tom Y. H., Brinker, Achim, Peters, Eric C., Hur, Wooyoung, Gray, Nathanael S., ...
In an attempt to better understand and control the processes that regulate stem cell fate, we have set out to identify small molecules that induce neuronal differentiation in embryonic stem cells...
Genome-scale functional profiling of the mammalian AP-1 signaling pathway
Chanda, Sumit K., White, Suhaila, Orth, Anthony P., Reisdorph, Richard, Miraglia, Loren, Thomas, Russell S., ...
Large-scale functional genomics approaches are fundamental to the characterization of mammalian transcriptomes annotated by genome sequencing projects. Although current high-throughput strategies...
Santoro, Stephen W., Anderson, J. Christopher, Lakshman, Vishva, Schultz, Peter G.
The addition of novel amino acids to the genetic code of Escherichia coli involves the generation of an aminoacyl-tRNA synthetase and tRNA pair that is ‘orthogonal’, meaning that it functions...
Structural evidence for substrate strain in antibody catalysis
Yin, Jun, Andryski, Scott E., Beuscher, Albert E., Stevens, Raymond C., Schultz, Peter G.
The crystal structure of the Michaelis complex between the Fab fragment of ferrochelatase antibody 7G12 and its substrate mesoporphyrin has been solved to 2.6-Å resolution. The antibody-bound...
An approach to genomewide screens of expressed small interfering RNAs in mammalian cells
Zheng, Lianxing, Liu, Jun, Batalov, Sergei, Zhou, Demin, Orth, Anthony, Ding, Sheng, ...
To facilitate the construction of large genomewide libraries of small interfering RNAs (siRNAs), we have developed a dual promoter system (pDual) in which a synthetic DNA encoding a gene-specific...
Identification of p53 regulators by genome-wide functional analysis
Huang, Qihong, Raya, Angel, DeJesus, Paul, Chao, Sheng-Hao, Quon, Kim C., Caldwell, Jeremy S., ...
The p53 tumor-suppressor protein is a critical mediator of cellular growth arrest and the induction of apoptosis. To identify proteins involved in the modulation of p53 transcriptional activity, a...
An expanded genetic code with a functional quadruplet codon
Anderson, J. Christopher, Wu, Ning, Santoro, Stephen W., Lakshman, Vishva, King, David S., Schultz, Peter G.
With few exceptions the genetic codes of all known organisms encode the same 20 amino acids, yet all that is required to add a new building block are a unique tRNA/aminoacyl-tRNA synthetase pair, a...
Selective incorporation of 5-hydroxytryptophan into proteins in mammalian cells
Zhang, Zhiwen, Alfonta, Lital, Tian, Feng, Bursulaya, Badry, Uryu, Sean, King, David S., ...
An orthogonal tryptophanyl–transfer RNA (tRNA) synthetase (TrpRS)-mutant opal suppressor tRNATrp (\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts}...
Torres, Francisco E., Kuhn, Peter, De Bruyker, Dirk, Bell, Alan G., Wolkin, Michal V., Peeters, Eric, ...
We report the fabrication of enthalpy arrays and their use to detect molecular interactions, including protein–ligand binding, enzymatic turnover, and mitochondrial respiration. Enthalpy arrays...
Liu, Jun, Bang, Anne G., Kintner, Chris, Orth, Anthony P., Chanda, Sumit K., Ding, Sheng, ...
The Wnt signaling pathway acts ubiquitously in metazoans to control various aspects of embryonic development. Wnt ligands bind their receptors Frizzled and low-density lipoprotein receptor-related...
An efficient rapid system for profiling the cellular activities of molecular libraries
Melnick, Jonathan S., Janes, Jeff, Kim, Sungjoon, Chang, Jim Y., Sipes, Daniel G., Gunderson, Drew, ...
Rapid quantitative methods for characterizing small molecules, peptides, proteins, or RNAs in a broad array of cellular assays would allow one to discover new biological activities associated with...
Collins, Cynthia S., Hong, Jiyong, Sapinoso, Lisa, Zhou, Yingyao, Liu, Zheng, Micklash, Kenneth, ...
Cell motility is a complex biological process, involved in development, inflammation, homeostasis, and pathological processes such as the invasion and metastatic spread of cancer. Here, we describe a...
Structural plasticity of an aminoacyl-tRNA synthetase active site
Turner, James M., Graziano, James, Spraggon, Glen, Schultz, Peter G.
Recently, tRNA aminoacyl-tRNA synthetase pairs have been evolved that allow one to genetically encode a large array of unnatural amino acids in both prokaryotic and eukaryotic organisms. We have...
siRNA in human cells selectively localizes to target RNA sites
Berezhna, Svitlana Y., Supekova, Lubica, Supek, Frantisek, Schultz, Peter G., Deniz, Ashok A.
Recent observations of RNA interference (RNAi) in the nuclei of human cells raise key questions about the extent to which nuclear and cytoplasmic RNAi pathways are shared. By directly visualizing the...
Single-molecule fluorescence spectroscopy of enzyme conformational dynamics and cleavage mechanism
Ha, Taekjip, Ting, Alice Y., Liang, Joy, Caldwell, W. Brett, Deniz, Ashok A., Chemla, Daniel S., ...
Fluorescence resonance energy transfer and fluorescence polarization anisotropy are used to investigate single molecules of the enzyme staphylococcal nuclease. Intramolecular fluorescence resonance...
Misregulation of gene expression in primary fibroblasts lacking poly(ADP-ribose) polymerase
Simbulan-Rosenthal, Cynthia M., Ly, Danith H., Rosenthal, Dean S., Konopka, Genevieve, Luo, RuiBai, Wang, Zhao-Qi, ...
Poly(ADP-ribose) polymerase (PARP) is implicated in the maintenance of genomic integrity, given that inhibition or depletion of this enzyme increases genomic instability in cells exposed to genotoxic...
Effects of environmental enrichment on gene expression in the brain
Rampon, Claire, Jiang, Cecilia H., Dong, Helin, Tang, Ya-Ping, Lockhart, David J., Schultz, Peter G., ...
An enriched environment is known to promote structural changes in the brain and to enhance learning and memory performance in rodents [Hebb, D. O. (1947) Am. Psychol. 2, 306–307]. To better...