A5049505423- Enzyme Structure and Function
- Microbial Natural Products and Biosynthesis
- Enzyme Production and Characterization
- RNA and protein synthesis mechanisms
- Genomics and Phylogenetic Studies
- Protein Structure and Dynamics
- Biochemical and Molecular Research
- Antibiotic Resistance in Bacteria
- Bacterial Genetics and Biotechnology
- Advanced Proteomics Techniques and Applications
- Microbial Metabolites in Food Biotechnology
- Peptidase Inhibition and Analysis
- Glycosylation and Glycoproteins Research
- Mass Spectrometry Techniques and Applications
- Amino Acid Enzymes and Metabolism
- Brucella: diagnosis, epidemiology, treatment
- Ion channel regulation and function
- Microbial Metabolic Engineering and Bioproduction
- Bacteriophages and microbial interactions
- Cancer Research and Treatments
- Escherichia coli research studies
- Microbial Metabolism and Applications
- Crystallization and Solubility Studies
- Machine Learning in Bioinformatics
- Monoclonal and Polyclonal Antibodies Research
Argonne National Laboratory
2015-2024
University of Chicago
2011-2024
Molecular Biology Consortium
2024
Seikagaku Corporation (Japan)
2023
Rigaku (Japan)
2023
Joint Center for Structural Genomics
2013-2023
Northwestern University
2023
Purdue University West Lafayette
2009
Pacific Northwest National Laboratory
2005-2009
Environmental Molecular Sciences Laboratory
2005
Abstract Direct-acting antivirals are needed to combat coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). The papain-like protease (PLpro) domain of Nsp3 from SARS-CoV-2 essential for viral replication. In addition, PLpro dysregulates the host immune response cleaving ubiquitin and interferon-stimulated gene 15 protein proteins. As a result, promising target inhibition small-molecule therapeutics. Here we design series...
The γ-proteobacterium Shewanella oneidensis strain MR-1 is a metabolically versatile organism that can reduce wide range of organic compounds, metal ions, and radionuclides. Similar to most other sequenced organisms, ≈40% the predicted ORFs in S. genome were annotated as uncharacterized “hypothetical” genes. We implemented an integrative approach by using experimental computational analyses provide more detailed insight into gene function. Global expression profiles determined for cells...
The New Delhi Metallo-β-lactamase (NDM-1) gene makes multiple pathogenic microorganisms resistant to all known β-lactam antibiotics. rapid emergence of NDM-1 has been linked mobile plasmids that move between different strains resulting in world-wide dissemination. Biochemical studies revealed is capable efficiently hydrolyzing a wide range β-lactams, including many carbapenems considered as "last resort" crystal structures metal-free apo- and monozinc forms presented here an enlarged...
The Drosophila trp (transient receptor potential) gene appears to encode the Drosophilastore-operated channel (SOC), and some mammalian homologues have been proposed SOCs. This study provides evidence for expression of three (Mtrp2, Mtrp3, Mtrp4) in fibroblasts from wild-type src knockout mice, four (Htrp1, Htrp3, Htrp4, Htrp6) human embryonic kidney (HEK-293) cells based on RT-PCR techniques. In HEK-293 stably transfected with a 323-bp Htrp3 antisense construct (Htrp3AS), Northern blot...
Significance There are many differences in the sequences of ketosynthase (KS) domains from well-studied type I polyketide synthases (PKSs) and more recently discovered acyltransferase (AT)-less PKSs. The AT-less PKSs generate polyketides with a high degree structural diversity, which stems their evolution by horizontal gene transfer. In comparison, canonical evolve duplication. seven structures PKS KSs reveal molecular details surrounding substrate specificity overall KSs. Understanding...
Terpenoids are the largest and most structurally diverse family of natural products found in nature, yet their presence bacteria is underappreciated. The carbon skeletons terpenoids generated through carbocation-dependent cyclization cascades catalyzed by terpene synthases (TSs). Type I type II TSs initiate via diphosphate ionization protonation, respectively, protein structures both types known. Most plant diterpene (DTSs) possess three α-helical domains (αβγ), which thought to have arisen...
We utilized 2-aminoethyoxydiphenyl borane, an agent that blocks store-operated Ca<sup>2+</sup> entry, as well antisense approach to characterize endogenous entry pathways in HEK-293 cells. The thapsigargin- and carbachol-induced, but not the 1-oleolyl-2-acytyl-<i>sn</i>-glycerol (OAG)-induced, was blocked by borane. Both reverse transcriptase-PCR Western blot analyses demonstrated expression for HTRP1, HTRP3, HTRP4 specific suppression of mRNA levels Trp protein cells stably expressing...
Lys-Bradykinin (BK), a mitogen for human foreskin fibroblasts (HSWP cells) (Owen, N. E., and Villereal, M. L. (1983) Cell 32, 979-985), elicits rapid, transient elevation of intracellular free Ca2+ concentration ([Ca2+]i) in these cells. We have used image analysis fura-2-loaded HSWP cells to examine the BK-induced [Ca2+]i changes individual BK-stimulated entry release stores can be distinguished by stimulating presence or absence extracellular Ca2+, inhibiting with 5 mM NiCl2. BK-sensitive...
Abstract The Bacillus subtilis KinD signal‐transducing histidine kinase is a part of the sporulation phosphorelay known to regulate important developmental decisions such as and biofilm formation. We have determined crystal structures extracytoplasmic sensing domain KinD, which was copurified crystallized with pyruvate ligand. structure ligand‐binding site mutant also determined; it an acetate segment similar that several other domains signal transduction proteins composed tandem...
Coupling microfluidics with microscopy has emerged as a powerful approach to study at cellular resolution the dynamics in plant physiology and root-microbe interactions (RMIs). Most devices have been designed model Arabidopsis thaliana higher throughput than conventional methods. However, there is need for microfluidic which enable vivo studies of root development RMIs woody plants. Here, we developed RMI-chip, simple setup Populus tremuloides (aspen tree) seedlings can grow over month,...
Abstract Serial x-ray crystallography can uncover binding events, and subsequent chemical conversions occurring during enzymatic reaction. Here, we reveal the structure, cleavage of moxalactam antibiotic bound to L1 metallo-β-lactamase (MBL) from Stenotrophomonas maltophilia . Using time-resolved serial synchrotron crystallography, show time course β-lactam hydrolysis determine ten snapshots (20, 40, 60, 80, 100, 150, 300, 500, 2000 4000 ms) at 2.20 Å resolution. The reaction is initiated by...
GELBANK is a publicly available database of two-dimensional gel electrophoresis (2DE) patterns proteomes from organisms with known genome information (available at http://gelbank.anl.gov and ftp://bioinformatics.anl.gov/gelbank/). Currently it includes 131 completed, mostly microbial the National Center for Biotechnology Information. A web interface allows upload 2D their annotation registered users. The images are organized by species, tissue type, separation method, sample type staining...
A global proteomic evaluation of the response Arthrobacter sp. strain FB24 to 5 and 20 mM Cr(VI) was conducted using both two-dimensional gel electrophoresis (2-DGE) liquid chromatography coupled with tandem mass spectrometry (LC/LC-MS/MS). The changes in protein expression found 2-DGE indicate alterations central metabolism amino acid synthesis. Proteome coverage increased from 22% 71% LC/LC-MS/MS. proteins exhibiting highest levels under stress suggest intracellular sulfur limitation,...
The human intestine harbors a large number of microbes forming complex microbial community that greatly affects the physiology and pathology host. In gut microbiome, enrichment in certain protein gene families appears to be widespread. They include enzymes involved carbohydrate metabolism such as glucoside hydrolases dietary polysaccharides glycoconjugates. We report crystal structures (wild type, 2 mutants, mutant/substrate complex) enzymatic activity recombinant α-glucosidase from...
In many cell types, G protein-coupled receptors stimulate a transient Ca2+ release from internal stores followed by sustained, capacitative entry, which is mediated store-operated channels (SOCs). Although it clear that SOCs are activated depletion of Ca2+stores, the mechanism for this process not well understood. Previously, we have reported inhibitors tyrosine kinase activity block bradykinin- and thapsigargin-stimulated entry in fibroblasts, suggesting may be involved relaying message...
ABSTRACT We present the crystal structure of extracytoplasmic domain Bacillus subtilis PhoR sensor histidine kinase, part a two-component system involved in adaptation to low environmental phosphate concentrations. In addition structure, we predict that majority domains B. kinases will adopt fold similar ubiquitous PAS domain.
ABSTRACT Carrier proteins (CPs) play a critical role in the biosynthesis of various natural products, especially nonribosomal peptide synthetase (NRPS) and polyketide synthase (PKS) enzymology, where CPs are referred to as peptidyl‐carrier (PCPs) or acyl‐carrier (ACPs), respectively. can either be domain large multifunctional polypeptides standalone proteins, termed Type I II, There have been many biochemical studies PKS NRPS CPs, II ACPs. However, recently number PCPs found biochemically...