A5091496526- Epigenetics and DNA Methylation
- Cancer-related gene regulation
- RNA modifications and cancer
- Genomics and Chromatin Dynamics
- Enzyme Structure and Function
- Histone Deacetylase Inhibitors Research
- Amino Acid Enzymes and Metabolism
- Metabolism and Genetic Disorders
- Circadian rhythm and melatonin
- Cancer, Hypoxia, and Metabolism
- Protein Structure and Dynamics
- RNA and protein synthesis mechanisms
- Polyamine Metabolism and Applications
- Biochemical and Molecular Research
- Chemical Synthesis and Analysis
- Cancer Research and Treatments
- Chemical Reactions and Isotopes
- Protein Degradation and Inhibitors
- Ubiquitin and proteasome pathways
- Fungal and yeast genetics research
- Metalloenzymes and iron-sulfur proteins
- Microbial Metabolic Engineering and Bioproduction
- Crystallography and molecular interactions
- Genetics, Aging, and Longevity in Model Organisms
- Mitochondrial Function and Pathology
University of Michigan
2015-2024
Regional West Medical Center
2008-2012
Ann Arbor Center for Independent Living
2011
Michigan United
2010
University of Kentucky
2007
National Institute of Diabetes and Digestive and Kidney Diseases
2003
National Institutes of Health
2002-2003
The Wistar Institute
1999-2000
University of Pennsylvania
1999-2000
University of Rochester
1999
The p53 tumor suppressor protein is a sequence-specific transcription factor that modulates the response of cells to DNA damage. Recent studies suggest full transcriptional activity requires coactivators CREB binding (CBP)/p300 and PCAF. These interact with each other, both possess intrinsic histone acetyltransferase activity. Furthermore, p300 acetylates activate its in vitro. In this study, we demonstrate PCAF also vitro at lysine residue distinct from acetylated by thereby increases p53's...
SET8 (also known as PR-SET7) is a histone H4-Lys-20-specific methyltransferase that implicated in cell-cycle-dependent transcriptional silencing and mitotic regulation metazoans. Herein we report the crystal structure of human (hSET8) bound to H4 peptide bearing Lys-20 product cofactor S-adenosylhomocysteine. Histone intercalates substrate-binding cleft an extended parallel β-strand. Residues preceding engage extensive array salt bridge, hydrogen bond, van der Waals interactions with hSET8,...
Within chromatin, reversible acetylation of core histones is critical for transcriptional activation eukaryotic target genes. The recent identification intrinsic histone acetyltransferase (HAT) catalytic activity from a number co-activators (including yeast GCN5, p300/CBP, P/CAF, and TAFII250), has underscored the importance protein in control. GCN5 family prototype diverse group at least four distinct human HATs families. Although there now clear link between vivo HAT gene activation,...
Pain associated with inflammation involves prostaglandins synthesized from arachidonic acid (AA) through cyclooxygenase-2 (COX-2) pathways while thromboxane A 2 formed by platelets AA via cyclooxygenase-1 (COX-1) mediates thrombosis. COX-1 and COX-2 are both targets of nonselective nonsteroidal antiinflammatory drugs (nsNSAIDs) including aspirin whereas activity is preferentially blocked inhibitors called coxibs. COXs homodimers composed identical subunits, but we have shown that only one...
Histone H3 lysine 4 (H3K4) methylation is catalyzed by the highly evolutionarily conserved multiprotein complex known as Set1/COMPASS or MLL/COMPASS-like complexes from yeast to human, respectively. Here we have reconstituted fully functional and human in vitro identified minimum subunit composition required for histone H3K4 methylation. These subunits include methyltransferase C-terminal SET domain of Set1/MLL, Cps60/Ash2L, Cps50/RbBP5, Cps30/WDR5, Cps25/Dpy30, which are all common...
Recent studies have demonstrated that carbon–oxygen (CH···O) hydrogen bonds important roles in S-adenosylmethionine (AdoMet) recognition and catalysis methyltransferases. Here, we investigate noncovalent interactions occur between the AdoMet sulfur cation oxygen atoms methyltransferase active sites. These represent sulfur–oxygen (S···O) chalcogen which atom donates a lone pair of electrons to σ antibonding orbital atom. Structural, biochemical, computational analyses an asparagine mutation...
The yeast GCN5 (yGCN5) transcriptional coactivator functions as a histone acetyltransferase (HAT) to promote activation. Here, we present the high resolution crystal structure of HAT domain yGCN5 and probe functional importance conserved glutamate residue. reveals central protein core associated with AcCoA binding that appears be structurally among superfamily N -acetyltransferases, including 1 Serratia marcescens aminoglycoside 3- -acetyltransferase. A pronounced cleft lying above this...
SET domain protein lysine methyltransferases (PKMTs) regulate transcription and other cellular functions through site-specific methylation of histones substrates. PKMTs catalyze the formation monomethylated, dimethylated, or trimethylated products, establishing an additional hierarchy with respect to methyllysine recognition in signaling. Biochemical studies have identified a conserved position within their active sites, Phe/Tyr switch, that governs respective product specificities. To...
S-Adenosylmethionine (AdoMet)-based methylation is integral to metabolism and signaling. AdoMet-dependent methyltransferases belong multiple distinct classes share a catalytic mechanism that arose through convergent evolution; however, fundamental determinants underlying this shared methyl transfer remain undefined. A survey of high-resolution crystal structures reveals unconventional carbon–oxygen (CH···O) hydrogen bonds coordinate the AdoMet group in different irrespective their class,...