A5074158847- Enzyme Structure and Function
- Enzyme Production and Characterization
- Cancer Research and Treatments
- Genomics and Phylogenetic Studies
- Microbial Metabolism and Applications
- Biochemical and Molecular Research
- RNA and protein synthesis mechanisms
- Glycosylation and Glycoproteins Research
- Microbial Natural Products and Biosynthesis
- Photosynthetic Processes and Mechanisms
- Cellular Mechanics and Interactions
- RNA modifications and cancer
- Protein Structure and Dynamics
- Bacterial Genetics and Biotechnology
- Machine Learning in Bioinformatics
- Peptidase Inhibition and Analysis
- ATP Synthase and ATPases Research
- Amino Acid Enzymes and Metabolism
- Microbial Metabolic Engineering and Bioproduction
- Molecular Biology Techniques and Applications
- Vibrio bacteria research studies
- Bacteriophages and microbial interactions
- Biotin and Related Studies
- Metabolism and Genetic Disorders
- Cardiomyopathy and Myosin Studies
Rutgers, The State University of New Jersey
2023-2024
Columbia University
2008-2022
Rensselaer Polytechnic Institute
2021
Structural Genomics Consortium
2012-2021
Saint Petersburg State Pediatric Medical University
2020
New York Structural Biology Center
2005-2017
Emory University
2003
University of California, Berkeley
2003
Albert Einstein College of Medicine
1998-2003
Florida State University
2002
Tryptophan 2,3-dioxygenase (TDO) and indoleamine (IDO) constitute an important, yet relatively poorly understood, family of heme-containing enzymes. Here, we report extensive structural biochemical studies the Xanthomonas campestris TDO a related protein SO4414 from Shewanella oneidensis , including structure at 1.6-Å resolution catalytically active, ferrous form in binary complex with substrate l -Trp. The carboxylate ammonium moieties tryptophan are recognized by electrostatic...
Nucleophilic catalysis is a general strategy for accelerating ester and amide hydrolysis. In natural active sites, nucleophilic elements such as catalytic dyads triads are usually paired with oxyanion holes substrate activation, but it difficult to parse out the independent contributions of these or understand how they emerged in course evolution. Here we explore minimal requirements esterase activity by computationally designing artificial catalysts using holes. We found much higher success...
The structures of Saccharomyces cerevisiae , Dictyostelium and Caenorhabditis elegans actin bound to gelsolin segment-1 have been solved refined at resolutions between 1.9 1.75 Å. These reveal several features relevant the ATP hydrolytic mechanism, including identification nucleophilic water roles Gln-137 His-161 in positioning activating catalytic water, respectively. involvement these residues mechanism is consistent with yeast genetics studies. This work highlights both structural...
The structure of profilin from the budding yeast Saccharomyces cerevisiae has been determined by X-ray crystallography at 2.3 Å resolution. overall fold is similar to observed for other structures. interactions and human platelet profilins with rabbit skeletal muscle actin were characterized titration microcalorimetry, fluorescence titrations, nucleotide exchange kinetics. affinity (2.9 μM) approximately 30-fold weaker than (0.1 μM), relative contributions entropic enthalpic terms free...
An antiparallel actin dimer has been proposed to be an intermediate species during filament nucleation. We now show that latrunculin A, a marine natural product inhibits polymerization, arrests polylysine-induced nucleation at the level of dimer, resulting in its accumulation. These dimers, when composed pyrene-labeled subunits, give rise fluorescent excimer, permitting detection polymerization <i>in vitro</i>. report crystallographic structure polylysine-actin-latrunculin A complex 3.5-Å...
Bacillus subtilis PaiA has been implicated in the negative control of sporulation as well production degradative enzymes. shares recognizable sequence homology with N-acetyltransferases, including those that can acetylate spermidine/spermine substrates. We have determined crystal structure complex CoA at 1.9 A resolution and found is a member N-acetyltransferase superfamily Unexpectedly, we observed binding an oxidized dimer active site PaiA, structural information suggests substrates enzyme...
ABSTRACT Cystic fibrosis (CF) is caused by mutations in a chloride channel called the human Fibrosis Transmembrane Conductance Regulator (hCFTR). We used cryo-EM global conformational ensemble reconstruction to characterize mechanism which breakthrough drug VX445 (Elexacaftor) simultaneously corrects both protein-folding and channel-gating defects CF mutations. drives hCFTR molecules harboring gating-defective G551D mutation towards open-channel conformation binding site first transmembrane...
The enzyme 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) lyase catalyzes the terminal steps in ketone body generation and leucine degradation. Mutations this cause a human autosomal recessive disorder called primary metabolic aciduria, which typically kills victims because of an inability to tolerate hypoglycemia. Here we present crystal structures HMG-CoA lyases from Bacillus subtilis Brucella melitensis at 2.7 2.3 Å resolution, respectively. These enzymes share greater than 45% sequence...
YhcB, a poorly understood protein conserved across gamma-proteobacteria, contains domain of unknown function (DUF1043) and an N-terminal transmembrane domain. Here, we used integrated approach including X-ray crystallography, genetics, molecular biology to investigate the structure YhcB. The Escherichia coli yhcB KO strain does not grow at 45 °C is hypersensitive cell wall-acting antibiotics, even in stationary phase. deletion leads filamentation, abnormal FtsZ ring formation, aberrant...
We have previously shown that monomeric globular αβ-proteins can be designed de novo with considerable control over topology, size, and shape. In this paper, we investigate the design of cyclic homo-oligomers from these starting points. experimented both keeping original monomer backbones fixed during docking process, allowing backbone to conform adjacent subunits in homo-oligomer. The latter flexible protocol generated designs shape complementarity approaching native homo-oligomers, but...
As a step towards better integrating protein three-dimensional (3D) structural information in cancer systems biology, the Northeast Structural Genomics Consortium (NESG) (www.nesg.org) has constructed Human Cancer Pathway Protein Interaction Network (HCPIN) by analysis of several classical cancer-associated signaling pathways and their physical protein-protein interactions.1 Many well-known proteins play central roles as "hubs" or "bottlenecks" HCPIN (http://nmr.cabm.rutgers.edu/hcpin). NESG...
SUMMARY Influenza A and B viruses overcome the host antiviral response to cause a contagious often severe human respiratory disease. Here, integrative structural biology biochemistry studies on non- protein 1 of influenza virus (NS1B) reveal previously unrecognized viral mechanism for innate immune evasion. Conserved basic groups its C-terminal domain (NS1B-CTD) bind 5’- triphosphorylated double-stranded RNA (5’ppp-dsRNA), primary pathogen-associated feature that activates retinoic...
This report presents a new approach to streak-seeding based on custom-designed silicon microtools. Experimental data show that the microtools produce similar results commonly used boar bristles. One advantage using is it rigid and can easily serve as an accurately calibrated end-effector micro-robotic system. Additionally, fabrication technology allows production of various shapes sizes. A working prototype automatic system these was built successfully applied for protein crystallization.