A5049610765- Malaria Research and Control
- RNA and protein synthesis mechanisms
- Mosquito-borne diseases and control
- Bacterial Genetics and Biotechnology
- Advanced Electron Microscopy Techniques and Applications
- Glycosylation and Glycoproteins Research
- Antibiotic Resistance in Bacteria
- Complement system in diseases
- Enzyme Structure and Function
- Biochemical effects in animals
- Drug Transport and Resistance Mechanisms
- Antimicrobial Resistance in Staphylococcus
- Carbohydrate Chemistry and Synthesis
- Biochemical and Molecular Research
- Diversity and Career in Medicine
- Monoclonal and Polyclonal Antibodies Research
- Characterization and Applications of Magnetic Nanoparticles
- Reproductive Health and Technologies
- ATP Synthase and ATPases Research
- Immune Response and Inflammation
- Machine Learning in Bioinformatics
- Escherichia coli research studies
- Ion Transport and Channel Regulation
- Amino Acid Enzymes and Metabolism
- Toxoplasma gondii Research Studies
Columbia University Irving Medical Center
2020-2025
Columbia University
2021
Novartis (United States)
2020
Novartis (Switzerland)
2019
Novartis Institutes for BioMedical Research
2019
University of California, Los Angeles
2018-2019
Protein Express (United States)
2008-2010
University of California, San Francisco
2010
Laboratoire de Biologie Physico-Chimique des Protéines Membranaires
2010
UConn Health
1977
In humans, NH 3 transport across cell membranes is facilitated by the Rh (rhesus) family of proteins. Human C glycoprotein (RhCG) forms a trimeric complex that plays an essential role in ammonia excretion and renal pH regulation. The X-ray crystallographic structure human RhCG, determined at 2.1 Å resolution, reveals mechanism transport. Each monomer contains 12 transmembrane helices, one more than bacterial homologs. Reconstituted into proteoliposomes, RhCG conducts to raise internal pH....
We describe here the isolation, purification, and structural characterization of a lipid A precursor synthesized under nonpermissive conditions by mutant Salmonella typhimurium conditionally defective in synthesis 3-deoxy-D-mannoctulosonate (2-keto-3-deoxyoctonate, KDO) region lipopolysaccharide. The was isolated free from lipopolysaccharide, murein, phospholipids extraction delipidated cells with 90% phenol/CHCL3/petroleum ether. molecule recovered phenol phase after precipitation...
The lipopolysaccharide biosynthesis pathway is considered an attractive drug target against the rising threat of multi-drug-resistant Gram-negative bacteria. Here, we report two novel small-molecule inhibitors (compounds 1 and 2) acyltransferase LpxA, first enzyme in pathway. We show genetically that antibacterial activities compounds efflux-deficient Escherichia coli are mediated by LpxA inhibition. Consistently, inhibited enzymatic reaction vitro. Intriguingly, using biochemical,...
Significance Malaria parasites invade and replicate within human red blood cells, which lack nuclei have minimal metabolic activity. To survive, the create new pathways that alter permeability of cell membrane, allowing them to import nutrients export waste. Here, we present native structure three-membered RhopH protein complex, plays a key role in this process. We determined essential complex from heterogeneous mixture proteins enriched directly parasite lysate, using cryo-electron...
The Plasmodium falciparum sodium efflux pump Pf ATP4 is a leading antimalarial target, but suffers from lack of high-resolution structural information needed to identify functionally important features in conserved regions and guide rational design next generation inhibitors. Here, we determine 3.7Å cryoEM structure purified CRISPR-engineered P. parasites, revealing previously unknown, apicomplexan-specific binding partner, ABP, which forms conserved, likely modulatory interaction with ATP4....
LpxD, acyl-ACP-dependent N-acyltransferase, is the third enzyme of lipid A biosynthesis in Gram-negative bacteria. recent probe-based screen identified several compounds, including 6359-0284 (compound 1), that inhibit enzymatic activity Escherichia coli (E. coli) LpxD. Here, we use these inhibitors to chemically validate LpxD as an attractive antibacterial target. We first found compound 1 was oxidized solution more stable aromatized tetrahydro-pyrazolo-quinolinone 1o. From strain deficient...
Abstract Malaria parasites rely heavily on rapid, high fidelity protein synthesis to infect and replicate in human erythrocytes, making translation an attractive target for new antimalarials. Here, we have determined situ structures of Pf 80S ribosomes thirteen conformational compositional states from cryoFIB-milled Plasmodium falciparum -infected erythrocytes across the stages asexual intraerythrocytic parasite replication. We observe eight active intermediates, enabling us define native...
Abstract The RhopH complex is implicated in malaria parasites’ ability to invade and create new permeability pathways host erythrocytes, but its mechanisms remain poorly understood. Here we enrich the endogenous a native soluble form, comprising RhopH2, CLAG3.1 RhopH3, directly from parasite cell lysates determine atomic structure using cryo electron microscopy, mass spectrometry, cryoID program. This first direct observation of an exported P. falciparum transmembrane protein—in soluble,...
Drs. Monica Mugnier and Chi-Min Ho work in the field of parasitology.
The lipopolysaccharide biosynthesis pathway is considered an attractive drug target against the rising threat of multidrug-resistant Gram-negative bacteria. Here, we report two novel small-molecule inhibitors (compounds 1 and 2) acyltransferase LpxA, first enzyme in pathway. We show genetically that antibacterial activities compounds efflux-deficient Escherichia coli are mediated by LpxA inhibition. Consistently, inhibited enzymatic reaction vitro. Intriguingly, using biochemical,...
The paper with the doi 10.1101/850305 has been removed as a result of technical error. is available on bioRxiv under this doi: 10.1101/2019.12.14.850305.