A5012376260- Regulation of Appetite and Obesity
- Pancreatic function and diabetes
- Ubiquitin and proteasome pathways
- Biochemical Analysis and Sensing Techniques
- RNA and protein synthesis mechanisms
- Adipose Tissue and Metabolism
- Peptidase Inhibition and Analysis
- Click Chemistry and Applications
- RNA Research and Splicing
- RNA modifications and cancer
- Protein Structure and Dynamics
- Monoclonal and Polyclonal Antibodies Research
- Biotin and Related Studies
- Chemical Synthesis and Analysis
- Protein Kinase Regulation and GTPase Signaling
- Lipid Membrane Structure and Behavior
- Endoplasmic Reticulum Stress and Disease
- Metabolism, Diabetes, and Cancer
- Enzyme Structure and Function
- Electrohydrodynamics and Fluid Dynamics
- Plant biochemistry and biosynthesis
- Neurobiology and Insect Physiology Research
- Biochemical and Structural Characterization
- Advanced Proteomics Techniques and Applications
- Diet, Metabolism, and Disease
Syracuse University
2016-2025
Living Systems (United States)
2022-2025
University of Georgia
2021
University of Michigan
2009-2012
Purdue University West Lafayette
2009-2012
Michigan United
2011
Howard Hughes Medical Institute
2004-2008
University of Chicago
2001-2008
Northwestern University
2000
We report a method that uses the process of selective withdrawal one fluid through second immiscible to coat small particles with polymer films. Fluid is withdrawn tube its orifice slightly above water-oil interface. Upon increasing flow rate, there transition from state where only oil water, containing be coated and appropriate prepolymer reagents, entrained in thin spout along oil. The eventually cause interface break, producing controllable thickness around each particle, which can...
Farnesylation is an important post-translational modification catalyzed by farnesyltransferase (FTase). Until recently it was believed that a C-terminal CaaX motif required for farnesylation, but recent experiments have revealed larger substrate diversity. In this study, we propose general structural modeling scheme to account peptide binding specificity and recapitulate the experimentally derived selectivity profile of FTase in vitro. addition highly accurate recovery known targets, also...
Ghrelin O-acyltransferase (GOAT) is an integral membrane acyltransferase responsible for catalyzing a serine-octanoylation posttranslational modification within the peptide hormone ghrelin. requires this octanoylation its biological activity in stimulating appetite and regulating other physiological pathways involved energy balance. Blocking ghrelin acylation using GOAT inhibitors new potential avenue to treat health conditions impacted by signaling, such as obesity diabetes. Designing novel...
The viability of living systems depends inextricably on enzymes that catalyze phosphoryl transfer reactions. For many in this class, including several ribozymes, divalent metal ions serve as obligate cofactors. Understanding how mediate catalysis requires elucidation ion interactions with both the enzyme and substrate(s). In Tetrahymena group I intron, previous work using atomic mutagenesis quantitative analysis rescue behavior identified three (MA, MB, MC) make five ribozyme substrates...
Ras GTPases and other CaaX proteins undergo multiple post-translational modifications at their carboxyl-terminus. These events initiate with prenylation of a cysteine are followed by endoproteolytic removal the 'aaX' tripeptide carboxylmethylation. Some only subject to prenylation, however, due presence an uncleavable sequence. In this study, sequences were used stage isoforms in farnesylated uncleaved state address impact proteolysis on protein localization function. This targeted strategy...
Ghrelin is a 28 amino acid peptide hormone that impacts wide range of biological processes, including appetite regulation, glucose metabolism, growth and cognitive function. To bind activate its cognate receptor, ghrelin must be acylated on serine residue in post-translational modification performed by O-acyltransferase (GOAT). GOAT membrane-bound (MBOAT) responsible for the catalysis addition an octanoyl fatty to third desacyl ghrelin. Beyond canonical role maturation endocrine cells within...
Geranylgeranylation is a critical post-translational modification essential for various cellular functions. However, current methods synthesizing geranylgeranylated proteins are complex and costly, which hinders access to these both biophysical biomaterials applications. Here, we present method the one-pot production of in Escherichia coli. We engineered E. coli express geranylgeranyl pyrophosphate synthase (GGS), an enzyme that catalyzes pyrophosphate. By coexpressing GGS with...
Abstract Ghrelin is a gastric‐derived peptide hormone with demonstrated impact on alcohol intake and craving, but the reverse side of this bidirectional link, that is, effects ghrelin system, remains to be fully established. To further characterize relationship, we examined (1) levels via secondary analysis human laboratory administration experiments heavy‐drinking participants; (2) expression ghrelin, receptor, ghrelin‐O‐acyltransferase (GOAT) genes ( GHRL , GHSR MBOAT4 respectively) in...
Prenylation is a posttranslational modification whereby C-terminal lipidation leads to protein localization membranes. A "Ca(1)a(2)X" sequence has been proposed as the recognition motif for two prenylation enzymes, farnesyltransferase (FTase) and geranylgeranyltransferase type I. To define parameters involved in of a(2) residue, we performed structure-activity analysis which indicates that FTase discriminates between peptide substrates based on both hydrophobicity steric volume side chain at...
Site-specific protein labeling is an important technique in chemistry and used for diverse applications ranging from creating conjugates to immobilization. Enzymatic reactions, including prenylation, have been widely exploited as methods accomplish site-specific labeling. prenylation catalyzed by prenyltransferases, farnesyltransferase (PFTase) geranylgeranyltransferase type I (GGTase-I), both of which recognize C-terminal CaaX motifs with different specificities transfer prenyl groups...
The peptide hormone ghrelin plays a key role in regulating hunger and energy balance within the body. Ghrelin signaling presents promising unexploited target for development of small molecule therapeutics treatment obesity, diabetes, other health conditions. Inhibition O-acyltransferase (GOAT), which catalyzes an essential octanoylation step maturation, offers potential avenue controlling signaling. Through screening library, we have identified class synthetic triterpenoids that efficiently...
In 1968, Leslie Orgel and Francis Crick wrote back-to-back articles in the Journal of Molecular Biology , making same controversial point: that RNA could, because it could adopt structure (at time, tRNA was known to its famous “cloverleaf” secondary structure) (Fig. 1), act functionally as a catalyst (Crick 1968; 1968). Thereby, solution chicken-and-egg problem origin life proposed. Instead having coevolve an information carrier (such DNA) functional macromolecule proteins) copy from...
Multicellular biology is dependent on the control of cell-cell interactions. These concepts have begun to be exploited for engineering cell-based therapies. Herein, we detail use a multivalent lipidated scaffold rapid and reversible manipulation Chemically self-assembled nanorings (CSANs) are formed via oligomerization bivalent dihydrofolate reductase (DHFR2) fusion proteins using chemical dimerizer, bis-methotrexate. With targeting fused onto DHFR2 monomers, CSANs can target specific...
Protein prenylation is a posttranslational modification involving the attachment of C15 or C20 isoprenoid group to cysteine residue near C-terminus target substrate by protein farnesyltransferase (FTase) geranylgeranyltransferase type I (GGTase-I), respectively. Both these prenyltransferases recognize C-terminal "CaaX" sequence in their substrates, but recent studies yeast- and mammalian-based systems have demonstrated FTase can also accept sequences that diverge length from canonical...