A5039479636- Metal-Catalyzed Oxygenation Mechanisms
- Metalloenzymes and iron-sulfur proteins
- Metal complexes synthesis and properties
- Microbial metabolism and enzyme function
- CO2 Reduction Techniques and Catalysts
- Enzyme Structure and Function
- RNA modifications and cancer
- Porphyrin Metabolism and Disorders
- Metabolism and Genetic Disorders
- Biochemical and Molecular Research
- Microbial Natural Products and Biosynthesis
- Photosynthetic Processes and Mechanisms
- Heme Oxygenase-1 and Carbon Monoxide
- Hemoglobin structure and function
- DNA Repair Mechanisms
- RNA and protein synthesis mechanisms
- DNA and Nucleic Acid Chemistry
- Infective Endocarditis Diagnosis and Management
- Cancer, Hypoxia, and Metabolism
- Chemical Synthesis and Analysis
- Amino Acid Enzymes and Metabolism
- Advanced biosensing and bioanalysis techniques
- Studies on Chitinases and Chitosanases
- Mass Spectrometry Techniques and Applications
- Folate and B Vitamins Research
Pennsylvania State University
2016-2025
Northwestern University
2009-2014
California Institute of Technology
2005-2010
Northwest University
2010
Pomona College
2007
University of Utah
2005
Abstract Technologically critical rare-earth elements are notoriously difficult to separate, owing their subtle differences in ionic radius and coordination number 1–3 . The natural lanthanide-binding protein lanmodulin (LanM) 4,5 is a sustainable alternative conventional solvent-extraction-based separation 6 Here we characterize new LanM, from Hansschlegelia quercus ( Hans -LanM), with an oligomeric state sensitive radius, the lanthanum(III)-induced dimer being >100-fold tighter than...
MutY and endonuclease III, two DNA glycosylases from Escherichia coli, AfUDG, a uracil glycosylase Archeoglobus fulgidus, are all base excision repair enzymes that contain the [4Fe-4S](2+) cofactor. Here we demonstrate that, when bound to DNA, these become redox-active; binding shifts redox potential of [4Fe-4S](3+/2+) couple range characteristic high-potential iron proteins activates toward oxidation. Electrochemistry on DNA-modified electrodes reveals potentials for Endo III AfUDG 58 95 mV...
The transport of charge through the DNA base-pair stack offers a route to carry out redox chemistry at distance. Here we describe characteristics this that have been elucidated and how may be utilized within cell. shallow distance dependence associated with these reactions permits DNA-mediated signaling over long molecular distances in genome facilitates activation redox-sensitive transcription factors globally response oxidative stress. long-range funneling damage sites low oxidation...
The radical S-adenosyl-L-methionine (SAM) enzymes RlmN and Cfr methylate 23S ribosomal RNA, modifying the C2 or C8 position of adenosine 2503. methyl groups are installed by a two-step sequence involving initial methylation conserved Cys residue (RlmN Cys(355)) SAM. Methyl transfer to substrate requires reductive cleavage second equivalent Crystal structures with SAM show that single molecule coordinates [4Fe-4S] cluster. Residue Cys(355) is S-methylated located proximal group, suggesting...
Copper trafficking proteins, including the chaperone Atox1 and P1B-type ATPase ATP7B, have been implicated in cellular resistance to anticancer drug cisplatin. We determined two crystal structures of cisplatin-Atox1 adducts that reveal platinum coordination by conserved CXXC copper-binding motif. Direct interaction cisplatin with this functionally relevant site has significant implications for understanding molecular basis mediated copper transport pathways.
The class Ib ribonucleotide reductase of Escherichia coli can initiate reduction nucleotides to deoxynucleotides with either a Mn(III)2-tyrosyl radical (Y•) or Fe(III)2-Y• cofactor in the NrdF subunit. Whereas self-assemble from Fe(II)2-NrdF and O2, activation Mn(II)2-NrdF requires reduced flavoprotein, NrdI, proposed form oxidant for assembly by O2. crystal structures reported here E. reveal different coordination environments, suggesting distinct initial binding sites oxidants during...
Carbapenems Through the Looking Glass The carbapenem class of antibiotics is a critical weapon in ongoing fight against drug-resistant bacteria. Microbial biosynthesis these compounds, which contain strained β-lactam ring motif, proceeds via precursor that has wrong configuration at one carbons. Chang et al. (p. 1140 ) combined x-ray crystallography with multiple spectroscopic probes to map out mechanism by CarC enzyme inverts its mirror image.
Iron(II)- and 2-(oxo)-glutarate-dependent oxygenases catalyze diverse oxidative transformations that are often initiated by abstraction of hydrogen from carbon iron(IV)-oxo (ferryl) complexes. Control the relative orientation substrate C-H ferryl Fe-O bonds, primarily direction oxo group into one two cis-related coordination sites (termed inline offline), may be generally important for control reaction outcome. Neither complexes nor their fleeting precursors have been crystallographically...
Hydroxylation of aliphatic carbons by nonheme Fe(IV)-oxo (ferryl) complexes proceeds hydrogen-atom (H•) transfer (HAT) to the ferryl and subsequent coupling between carbon radical Fe(III)-coordinated oxygen (termed rebound). Enzymes that use H•-abstracting for other transformations must either suppress rebound or further process hydroxylated intermediates. For olefin-installing C–C desaturations, it has been proposed a second HAT Fe(III)–OH complex from α preempts rebound. Deuterium (2H) at...
Abstract Drug‐induced proteome stress that involves protein aggregation may cause adverse effects and undermine the safety profile of a drug. Safety drugs is regularly evaluated using cytotoxicity assays measure cell death. However, these provide limited insights into presence in live cells. A fluorogenic sensor reported to detect drug‐induced prior An prone Halo‐tag mutant (AgHalo) was evolved sense through its aggregation. Detection such conformational changes enabled by ligand fluoresces...
Archaea synthesize isoprenoid-based ether-linked membrane lipids, which enable them to withstand extreme environmental conditions, such as high temperatures, salinity, and low or pH values1-5. In some archaea, Methanocaldococcus jannaschii, these lipids are further modified by forming carbon-carbon bonds between the termini of two lipid tails within one glycerophospholipid generate macrocyclic archaeol from glycerophospholipids macrocycle glycerol dibiphytanyl tetraether (GDGT)1,2. GDGT...
DNA charge transport (CT) chemistry provides a route to carry out oxidative damage from distance in reaction that is sensitive mismatches and lesions. Here, DNA-mediated CT also leads oxidation of DNA-bound base excision repair enzyme, MutY. Ru(III), generated through flash/quench technique, found promote the [4Fe-4S] 2+ cluster MutY 3+ its decomposition product [3Fe-4S] 1+ . Flash/quench experiments monitored by EPR spectroscopy reveal spectra with g = 2.08, 2.06, 2.02, characteristic...
Base excision repair (BER) enzymes maintain the integrity of genome, and in humans, BER mutations are associated with cancer. Given remarkable sensitivity DNA-mediated charge transport (CT) to mismatched damaged base pairs, we have proposed that DNA glycosylases (EndoIII MutY) containing a redox-active [4Fe4S] cluster could use CT signaling one another search cooperatively for damage genome. Here, examine this model, where estimate electron transfers over few hundred pairs sufficient rapid...
Electrochemical DNA-based sensors that exploit the inherent sensitivity of DNA-mediated charge transport (CT) to base pair stacking perturbations are capable detecting mismatches and some common damage products. Here, using DNA-modified gold electrodes, monitoring electrocatalytic reduction DNA-bound methylene blue, we examine a wide range analogues DNA Among those detected products O4-methyl-thymine, O6-methyl-guanine, 8-oxo-guanine, 5-hydroxy-cytosine, as well therapeutic base, nebularine....
Enzymatic installation of chlorine/bromine into unactivated carbon centers provides a versatile, selective, and environmentally friendly alternative to chemical halogenation. Iron(II) 2-(oxo)-glutarate (FeII/2OG)-dependent halogenases are powerful biocatalysts that capable cleaving aliphatic C–H bonds introduce useful functional groups, including halogens. Using the structure Fe/2OG halogenase, WelO5, in complex with its small molecule substrate, we identified similar N-acyl amino acid...
The design of fluorogenic probes for a Halo tag is highly desirable but challenging. Previous work achieved this goal by controlling the chemical switch spirolactones upon covalent conjugation between and or incorporating "channel dye" into substrate binding tunnel tag. In work, we have developed novel class Halo-tag that are derived from solvatochromic fluorophores. optimal probe, harboring benzothiadiazole scaffold, exhibits 1000-fold fluorescence enhancement reaction with Structural,...
An RNA methylase caught in the act methylation is important function and antibiotic resistance. The RlmN a dual-specificity enzyme that can on ribosomal transfer (tRNA). radical S-adenosylmethionine (SAM) enzyme, which produces protein/RNA cross-linked intermediate. Schwalm et al. determined structure of to tRNA substrate found recognizes overall shape tRNA. Then it remodels anticodon region access base methylates. remodeling activity likely be key enzyme's dual specificity. Science , this...
The iron-dependent oxidase UndA cleaves one C3-H bond and the C1-C2 of dodecanoic acid to produce 1-undecene CO2. A published X-ray crystal structure showed that has a heme-oxygenase-like fold, thus associating it with structural superfamily includes known postulated non-heme diiron proteins, but revealed only single iron ion in active site. Mechanisms proposed for initiation decarboxylation by cleavage using monoiron cofactor activate O2 necessarily invoked unusual or potentially unfeasible...