A5055128033- Enzyme Structure and Function
- RNA and protein synthesis mechanisms
- Bacterial Genetics and Biotechnology
- Protein Structure and Dynamics
- Biochemical and Molecular Research
- Antibiotic Resistance in Bacteria
- Bacteriophages and microbial interactions
- Escherichia coli research studies
- Advancements in Photolithography Techniques
- CRISPR and Genetic Engineering
- Epigenetics and DNA Methylation
- Microbial Natural Products and Biosynthesis
- SARS-CoV-2 and COVID-19 Research
- DNA Repair Mechanisms
- Vibrio bacteria research studies
- Brucella: diagnosis, epidemiology, treatment
- Amino Acid Enzymes and Metabolism
- Microbial bioremediation and biosurfactants
- Microbial Metabolic Engineering and Bioproduction
- Cytomegalovirus and herpesvirus research
- Estrogen and related hormone effects
- Genomics and Phylogenetic Studies
- Pharmacogenetics and Drug Metabolism
- Glycosylation and Glycoproteins Research
- Tuberculosis Research and Epidemiology
University of Chicago
2014-2025
Argonne National Laboratory
2016-2025
Molecular Biology Consortium
2025
Siemens (United States)
2022-2024
University of South Florida
2024
Joint Center for Structural Genomics
2011-2023
Rural Development Administration
2009-2021
Stanford University
2021
Mentor Technologies
2019-2020
Northwestern University
2020
On the histone H3 tail, Lys 9 and 27 are both methylation sites associated with epigenetic repression, reside within a highly related sequence motif ARKS. Here we show that chromodomain proteins Polycomb (Pc) HP1 ( h eterochromatin p rotein 1 ) discriminatory for binding to these in vivo vitro. In Drosophila S2 cells, on polytene chromosomes, methyl-Lys Pc excluded from areas enriched HP1. Swapping of regions is sufficient switching nuclear localization patterns factors, indicating role...
The pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) continues to expand. Papain-like protease (PLpro) is one of two SARS-CoV-2 proteases potentially targetable with antivirals. PLpro an attractive target because it plays essential role in cleavage and maturation viral polyproteins, assembly the replicase-transcriptase complex, disruption host responses. We report a substantive body structural, biochemical, virus replication studies that identify several...
Abstract Severe Acute Respiratory Syndrome coronavirus 2 (SARS‐CoV‐2) is rapidly spreading around the world. There no existing vaccine or proven drug to prevent infections and stop virus proliferation. Although this similar human animal SARS‐CoVs Middle East (MERS‐CoVs), detailed information about SARS‐CoV‐2 proteins structures functions urgently needed develop effective vaccines, antibodies, antivirals. We applied high‐throughput protein production structure determination pipeline at Center...
Abstract SARS-CoV-2 Nsp15 is a uridine-specific endoribonuclease with C-terminal catalytic domain belonging to the EndoU family that highly conserved in coronaviruses. As activity seems be responsible for interference innate immune response, emerges as an attractive target therapeutic intervention. Here we report first structures bound nucleotides and show how enzyme specifically recognizes uridine moiety. In addition site present evidence second base binding can accommodate any base. The...
4397MetricsTotal Downloads439Last 6 Months80Last 12 Months143Total Citations7Last Months0Last Months0View all metrics
Ubiquitous bacteria from the genus Oleispira drive oil degradation in largest environment on Earth, cold and deep sea. Here we report genome sequence of antarctica show that compared with Alcanivorax borkumensis—the paradigm mesophilic hydrocarbonoclastic bacteria—O. has a larger witnessed massive gene-transfer events. We identify an array alkane monooxygenases, osmoprotectants, siderophores micronutrient-scavenging pathways. also at low temperatures, main protein-folding machine Cpn60...
Among 15 nonstructural proteins (Nsps), the newly emerging Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) encodes a large, multidomain Nsp3. One of its units is ADP-ribose phosphatase domain (ADRP; also known as macrodomain, MacroD), which believed to interfere with host immune response. Such function appears be linked ability protein remove from ADP-ribosylated and RNA, yet precise role molecular targets enzyme remain unknown. Here, five high-resolution (1.07–2.01 Å) crystal...
The specter of a return to an era in which infectious disease looms as significant threat human health is not just hyperbole; there are serious concerns about the widespread overuse and misuse antibiotics contributing increased antibiotic resistance pathogens. recent discovery new enzyme, first identified Klebsiella pneumoniae from patient New Delhi denoted NDM-1, represents example extreme promiscuity: It hydrolyzes inactivates nearly all known β-lactam-based with startling efficiency....
Activation of the IκB kinase (IKK) is central to NF-κB signaling. However, precise activation mechanism by which catalytic IKK subunits gain ability induce transcriptional activity not well understood. Here we report a 4 Å x-ray crystal structure human IKK2 (hIKK2) in its catalytically active conformation. The hIKK2 domain architecture closely resembles that Xenopus (xIKK2). whereas inactivated xIKK2 displays closed dimeric structure, dimers adopt open conformations permit higher order...
Abstract The xeroderma pigmentosum C (XPC) complex initiates nucleotide excision repair by recognizing DNA lesions before recruiting downstream factors. How XPC detects structurally diverse embedded within normal is unknown. Here we present a crystal structure that captures the yeast orthologue (Rad4) on single register of undamaged DNA. shows disulphide-tethered Rad4 flips out nucleotides and adopts conformation similar to seen with damaged Contrary many enzymes can directly reject...
Abstract SARS-CoV-2 is a member of the coronaviridae family and etiological agent respiratory Coronavirus Disease 2019. The virus has spread rapidly around world resulting in over two million cases nearly 150,000 deaths as April 17, 2020. Since no treatments or vaccines are available to treat COVID-19 SARS-CoV-2, complications derived from infections have overwhelmed healthcare systems world. This related SARS-CoV-1, that caused 2002-2004 outbreak Severe Acute Respiratory Syndrome. In...
Significance The 2′-O methyl group in Cap-1 is essential to protect viral RNA from host interferon-induced response. We determined crystal structures of SARS-CoV-2 Nsp10/16 heterodimer complex with substrates (Cap-0 analog and S-adenosyl methionine) products (Cap-1 S-adenosyl-L-homocysteine) at room temperature using synchrotron serial crystallography. Analysis these will aid structure-based drug design against 2′-O-methyltransferase SARS-CoV-2.
Type VII secretion systems are membrane-embedded nanomachines used by Gram-positive bacteria to export effector proteins from the cytoplasm extracellular environment. Many of these effectors polymorphic toxins comprised an N-terminal Leu-x-Gly (LXG) domain unknown function and a C-terminal toxin that inhibits growth bacterial competitors. In recent work, it was shown LXG require two cognate Lap for T7SS-dependent export. Here, we present 2.6 Å structure TelA opportunistic pathogen
Inosine 5′-monophosphate dehydrogenase (IMPDH) is a promising antibiotic target. This enzyme catalyzes the NAD-dependent oxidation of inosine (IMP) to xanthosine (XMP), which rate-limiting step in guanine nucleotide biosynthesis. Bacterial IMPDH-specific inhibitors have been developed that bind NAD+ site. These display varied affinities different bacterial IMPDHs are not easily rationalized by X-ray crystal structures enzyme–inhibitor complexes. Inspection 25 complexes, including 10 newly...