A5037553320- Glycosylation and Glycoproteins Research
- Protein Structure and Dynamics
- Carbohydrate Chemistry and Synthesis
- Bacterial Genetics and Biotechnology
- Enzyme Structure and Function
- RNA and protein synthesis mechanisms
- Retinoids in leukemia and cellular processes
- Bacteriophages and microbial interactions
- Receptor Mechanisms and Signaling
- Antibiotic Resistance in Bacteria
- Neuroscience and Neuropharmacology Research
- Drug Transport and Resistance Mechanisms
- Biochemical and Molecular Research
- Enzyme Production and Characterization
- Malaria Research and Control
- Monoclonal and Polyclonal Antibodies Research
- Lipid Membrane Structure and Behavior
- Ion channel regulation and function
- Metabolism and Genetic Disorders
- Amino Acid Enzymes and Metabolism
- Porphyrin Metabolism and Disorders
- Tuberculosis Research and Epidemiology
- Antioxidant Activity and Oxidative Stress
- Microbial Metabolites in Food Biotechnology
- SARS-CoV-2 and COVID-19 Research
Columbia University
2016-2025
Columbia University Irving Medical Center
2019-2025
UConn Health
2015
Albany Medical Center Hospital
2015
Institute of Molecular Biology and Biophysics
2007
Howard Hughes Medical Institute
1998-2007
MRC Laboratory of Molecular Biology
1996-1999
University of Cambridge
1999
University of Pavia
1994
Background: Methylmalonyl CoA mutase catalyses the interconversion of succinyl and methylmalonyl via a free radical mechanism. The enzyme belongs to family enzymes that catalyse intramolecular rearrangement reactions in which group hydrogen atom on adjacent carbons are exchanged. These use cofactor adenosylcobalamin (coenzyme B12) breaks form an adenosyl radical, thus initiating reaction. Determination structure substrate-free was initiated provide further insight into mechanism...
In most sensory systems, peripheral neurons project axons to precise locations in the brain create an internal representation of external world. mammals, individual olfactory express only one ∼1000 odorant receptor genes, such that are functionally distinct ([
Crystal structure analyses for biological macromolecules without known structural relatives entail solving the crystallographic phase problem. Typical de novo evaluations depend on incorporating heavier atoms than those found natively; most commonly, multi- or single-wavelength anomalous diffraction (MAD SAD) experiments exploit selenomethionyl proteins. Here, we realize routine determination using intrinsic scattering from native macromolecules. We devised robust procedures enhancing...
Vitamin A homeostasis is critical to normal cellular function. Retinol-binding protein (RBP) the sole specific carrier in bloodstream for hydrophobic retinol, main form which vitamin transported. The integral membrane receptor STRA6 mediates uptake of by recognizing RBP-retinol trigger release and internalization retinol. We present structure zebrafish determined 3.9-angstrom resolution single-particle cryo-electron microscopy. has one intramembrane nine transmembrane helices an intricate...
Abstract Human transferrin receptor 1 (CD71) guarantees iron supply by endocytosis upon binding of iron-loaded and ferritin. Arenaviruses the malaria parasite exploit CD71 for cell invasion epitopes on interaction with pathogenic hosts were identified. Here, we provide molecular basis ectodomain-human ferritin determining 3.9 Å resolution single-particle cryo-electron microscopy structure their complex validating our structural findings in a cellular context. The contact surfaces between...
Polymyxins are antibiotics used in the last line of defense to combat multidrug-resistant infections by Gram-negative bacteria. Polymyxin resistance arises through charge modification bacterial outer membrane with attachment cationic sugar 4-amino-4-deoxy-l-arabinose lipid A, a reaction catalyzed integral lipid-to-lipid glycosyltransferase 4-amino-4-deoxy-L-arabinose transferase (ArnT). Here, we report crystal structures ArnT from Cupriavidus metallidurans, alone and complex carrier...
The HCN1–4 channel family is responsible for the hyperpolarization-activated cation current If/Ih that controls automaticity in cardiac and neuronal pacemaker cells. We present cryoelectron microscopy (cryo-EM) structures of HCN4 presence or absence bound cAMP, displaying pore domain closed open conformations. Analysis cAMP-bound -unbound sheds light on how ligand-induced transitions cytosolic portion mediate effect cAMP gating highlights regulatory role a Mg2+ coordination site formed...
X-ray crystal structures of methylmalonyl-CoA mutase in complexes with substrate and inhibitors 2-carboxypropyl-CoA 3-carboxypropyl-CoA (substrate product analogues) show that the enzyme−substrate interactions change little during course rearrangement reaction, contrast to large conformational on binding. The complex shows a 5'-deoxyadenine molecule active site, bound weakly not attached cobalt atom coenzyme B12, rotated shifted from its position substrate-free adenosylcobalamin complex....
G‐protein‐coupled receptors (GPCRs) respond to external stimuli by activating heterotrimeric G proteins inside the cell. There is increasing evidence that many GPCRs exist as dimers or higher oligomers, but biochemical nature of such and what roles they have, if any, in signal transduction remains unclear. We conducted a comprehensive study dimerization 5HT2c serotonin receptor using disulphide‐trapping experiments. found dimer interface between transmembrane (TM) helices IV V markedly...
G protein–coupled receptors (GPCRs) are a prominent class of plasma membrane proteins that regulate physiologic responses to wide variety stimuli and therapeutic agents. Although GPCR oligomerization has been studied extensively in recombinant cells, it remains uncertain whether native expressed their natural cellular environment monomers, dimers, or oligomers. The goal this study was determine the monomer/oligomer status endogenously its environment. Native 5-HT<sub>2C</sub> choroid plexus...
Abstract Integral membrane transporters of the Mycobacterial Membrane Protein Large (MmpL) family and their interactome play important roles in synthesis export mycobacterial outer lipids. Despite current interest mycolic acid transporter, MmpL3, from perspective drug discovery, nature biological significance its remain largely unknown. We here report on a genome-wide screening by two-hybrid system for MmpL3 binding partners. While surprisingly low number proteins involved biosynthesis was...
Polymyxin resistance (PR) threatens the treatment of carbapenem-resistant Klebsiella pneumoniae (CRKP) infections. PR frequently arises through chemical modification lipid A portion lipopolysaccharide. Various mutations are implicated in PR, including three two-component systems—CrrA/B, PmrA/B, and PhoP/Q—and negative regulator MgrB. Few have been functionally validated. Therefore, here we adapt a CRISPR-Cas9 system to CRKP elucidate how clinical isolates induce PR. We demonstrate that CrrB...