A5010550612- DNA Repair Mechanisms
- DNA and Nucleic Acid Chemistry
- RNA and protein synthesis mechanisms
- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Mycotoxins in Agriculture and Food
- Enzyme Structure and Function
- Protein Structure and Dynamics
- Pharmacogenetics and Drug Metabolism
- HIV/AIDS drug development and treatment
- Microbial Natural Products and Biosynthesis
- RNA modifications and cancer
- RNA Research and Splicing
- Advanced biosensing and bioanalysis techniques
- Crystallography and molecular interactions
- Bacterial Genetics and Biotechnology
- Cellular transport and secretion
- Alzheimer's disease research and treatments
- Hemoglobin structure and function
- Drug Transport and Resistance Mechanisms
- Inflammatory mediators and NSAID effects
- Synthesis and Biological Evaluation
- Polyamine Metabolism and Applications
- Plant biochemistry and biosynthesis
- Carcinogens and Genotoxicity Assessment
Vanderbilt University
2015-2025
Averett University
2021
Vanderbilt-Ingram Cancer Center
2018-2020
Oregon Health & Science University
2005-2006
University of Minnesota
2005
National Center for Toxicological Research
1999
University of Mississippi
1995
Toughing It Out in Membranes The formation of crosslinks the triple-helical structure collagen is crucial to its function. In case IV, which provides structural integrity basement membrane animal tissues, chemical nature has been difficult pin down. Vanacore et al. (p. 1230 ) report a combination high-resolution mass spectrometric and nuclear magnetic resonance studies that establish crosslink between hydroxylysine-211 methionine-93 sulfimine group (-S=N-). This type bond appears have...
Cytochrome P450 158A2 (CYP158A2) is encoded within a three-gene operon (sco1206-sco1208) in the prototypic soil bacterium Streptomyces coelicolor A3(2). This widely conserved among streptomycetes. CYP158A2 has been suggested to produce polymers of flaviolin, pigment that may protect microbes from UV radiation, combination with adjacent rppA gene, which encodes type III polyketide synthase, 1,3,6,8-tetrahydroxynaphthalene synthase. Following cloning, expression, and purification this...
5-Hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC) form during active demethylation of 5-methylcytosine (5mC) are implicated in epigenetic regulation the genome. They differentially processed by thymine DNA glycosylase (TDG), an enzyme involved 5mC. Three modified Dickerson-Drew dodecamer (DDD) sequences, amenable to crystallographic spectroscopic analyses containing 5'-CG-3' sequence associated with genomic cytosine methylation, 5hmC, 5fC, or 5caC placed...
Lipocalin family proteins have been shown to bind a vast array of small molecules and subsequently adapted selectively specific ligands. In this study, candesartan, an antihypertension drug, was identified mouse human siderocalin in biomolecular NMR experiments, allowing for structural insights into the candesartan-siderocalin interaction. The ligand binding site determined through integrative biology approach using silico docking guided by experiments. Building on structurally informed...
From the x-ray crystal structure of CYP158A2 (Zhao, B., Guengerich, F. P., Bellamine, A., Lamb, D. C., Izumikawa, M., Lei, L., Podust, L. Sundaramoorthy, Reddy, Kelly, S. Kalaitzis, J. Stec, D., Voehler, Falck, R., Moore, B. S., Shimada, T., and Waterman, M. R. (2005) <i>J. Biol. Chem.</i> 280, 11599-11607), one 18 cytochrome P450 (CYP) genes in actinomycete <i>Streptomyces coelicolor</i>, ordered active site water molecules (WAT505, WAT600, WAT640), hydroxyl groups substrate flaviolin were...
Aflatoxin B1 (AFB) epoxide forms an unstable N7 guanine adduct in DNA. The undergoes base-catalyzed ring opening to give a highly persistent formamidopyrimidine (FAPY) which exists as mixture of forms. Acid hydrolysis the FAPY gives base two separable but interconvertible that have been assigned by various workers functional, positional, or conformational isomers. Recently, this structural question became important when one major species DNA was found be potently mutagenic and other block...
The Notch transmembrane domain exhibits significant structural differences from that of the amyloid precursor protein.
How the distinctive lipid composition of mammalian plasma membranes impacts membrane protein structure is largely unexplored, partly because dearth isotropic model systems that contain abundant sphingolipids and cholesterol. This gap addressed by showing sphingomyelin cholesterol-rich (SCOR) mixtures with phosphatidylcholine can be cosolubilized n-dodecyl-β-melibioside to form bicelles. Small-angle X-ray neutron scattering, as well cryo-electron microscopy, demonstrate these assemblies are...
Biological transformations of polyunsaturated fatty acids often lead to chemically unstable products, such as the prostaglandin endoperoxides and leukotriene A(4) epoxide mammalian biology allene epoxides plants. Here, we report on enzymatic production a acid containing highly strained bicyclic four-carbon ring, moiety known previously only model compound for mechanistic studies in chemistry. Starting from linolenic (C18.3omega3), dual function protein cyanobacterium Anabaena PCC 7120 forms...
Abstract Complex II (CII) activity controls phenomena that require crosstalk between metabolism and signaling, including neurodegeneration, cancer metabolism, immune activation, ischemia-reperfusion injury. CII can be regulated at the level of assembly, a process leverages metastable assembly intermediates. The nature these intermediates how subunits transfer complexes remains unclear. In this work, we identify species containing SDHA subunit its factors, assign preferred temporal sequence...
The crotonaldehyde- and acetaldehyde-derived R- S-alpha-CH3-gamma-OH-1,N2-propanodeoxyguanosine adducts were monitored in single-stranded duplex oligodeoxynucleotides using NMR spectroscopy. In both instances, the cis trans diastereomers of alpha-CH3 gamma-OH groups underwent slow exchange, with being favored. oligodeoxynucleotides, aldehyde intermediates not detected spectroscopically, but their presence was revealed through formation N-terminal conjugates tetrapeptide KWKK. When annealed...
Human cytochrome P450 3A4 forms a series of minor testosterone hydroxylation products in addition to 6β‐hydroxytestosterone, the major product. One these, formed at next highest rate after 6β‐ and 2β‐hydroxy products, was identified as 1β‐hydroxytestosterone. This product characterized from mixture oxidation using an HPLC‐solid phase extraction‐cryoprobe NMR/time‐of‐flight mass spectrometry system, with estimated total ≈ 6 µg this Mass established formula C 19 H 29 O 3 (MH + 305.2080). The...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAdenine Adduct of Aflatoxin B1 EpoxideRajkumar S. Iyer, Markus W. Voehler, and Thomas M. HarrisCite this: J. Am. Chem. Soc. 1994, 116, 20, 8863–8869Publication Date (Print):October 1, 1994Publication History Published online1 May 2002Published inissue 1 October 1994https://pubs.acs.org/doi/10.1021/ja00099a001https://doi.org/10.1021/ja00099a001research-articleACS PublicationsRequest reuse permissionsArticle Views247Altmetric-Citations46LEARN ABOUT...
The adaptor protein 4 (AP4) complex (ϵ/β4/μ4/σ4 subunits) forms a non-clathrin coat on vesicles departing the trans-Golgi network. AP4 biology remains poorly understood, in stark contrast to wealth of molecular data available for related clathrin adaptors AP1 and AP2. is important human health because mutations any subunit cause severe neurological problems, including intellectual disability progressive spastic para- or tetraplegias. We have used range structural, biochemical biophysical...
Spectroscopic evidence is presented for the formation of a carbinolamine interchain cross-link in 5'-CpG-3' sequences, arising from acrolein adduct γ-OH-PdG. This may be important understanding biological processing acrolein-induced DNA damage CpG sequences.
The interstrand N 2,N 2-dG DNA cross-linking chemistry of the acrolein-derived γ-OH-1,N 2-propanodeoxyguanosine (γ-OH-PdG) adduct in 5‘-CpG-3‘ sequence was monitored within a dodecamer duplex by NMR spectroscopy, situ, using series site-specific 13C- and 15N-edited experiments. At equilibrium 40% cross-linked, with carbinolamine form cross-link predominating. existed non-crosslinked 2-(3-oxo-propyl)-dG aldehyde its geminal diol hydrate. ratio aldehyde/diol increased at higher temperatures....
Reaction of 2 equiv K[1,3-(SiMe3)2C3H3] with NiBr2(dme) in THF at −78 °C produces the orange π-allyl complex [1,3-(SiMe3)2C3H3]2Ni (1). Unlike pyrophoric (C3H5)2Ni, trimethylsilylated derivative only slowly decomposes air (from hours to days). Both eclipsed (1a) and staggered (1b) conformations are found solution; form irreversibly converts thermodynamically more stable conformation when heated above 85 °C. Single-crystal X-ray structures obtained for both 1a 1b confirm that allyl ligands...
3-(2'-Deoxy-beta-D-erythro-pentofuranosyl)pyrimido[1,2-alpha]purin-10(3H)-one (M1dG) is the major product of reaction deoxyguanosine with malondialdehyde (MDA). M1dG blocks replication by DNA polymerases in vitro and mutagenic vivo. reacts hydroxide to form N2-(3-oxo-1-propenyl)deoxyguanosine anion (N2OPdG-). This pH-dependent reverses under neutral acidic conditions M1dG. Here we describe kinetics mechanism ring-closure both nucleoside oligonucleotides. Kinetic analysis absorbance...
The guanine N7 adduct of aflatoxin B1 exo-8,9-epoxide hydrolyzes to form the formamidopyrimidine (AFB-FAPY) adduct, which interconverts between α and β anomers. anomer is highly mutagenic in Escherichia coli, producing G → T transversions; it thermally stabilizes DNA duplex. AFB-α-FAPY blocks replication; destabilizes Herein, structure has been elucidated 5′-d(C1T2A3T4X5A6T7T8C9A10)-3′·5′-d(T11G12A13A14T15C16A17T18A19G20)-3′ (X = AFB-α-FAPY) using molecular dynamics calculations restrained...