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- Keyword
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- 4-ethylenedioxythiophene) (PEDOT); Carbon fiber microelectrode; Peroxynitrite detection (1)
- Amish (1)
- Aromatase; COX-2 inhibitors; Sulfonanilides; SiRNA (1)
- Breast cancer; COX-2; Nimesulide; Aromatase suppressor (1)
- Bridging carbonyl (1)
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- DNA polymerases;Replication;Repair;Translesion DNA synthesis; Mutagenesis (1)
- DNA polymerization;Fidelity;Mutagenesis;Non-natural nucleotides;Hydrogen bonding interactions (1)
- DNA polymerization;Template-independent DNA synthesis;Fidelity;Recombination;Nucleotide analog (1)
- Genotyping and mapping (1)
- Gibbs' energy (1)
- H-cluster (1)
- Homozygosity (1)
- Hydrogenase; H-cluster; density functional theory; quantum mechanics/molecular mechanics calculations; Gibbs’ energy; bridging carbonyl; terminal carbonyl; residue substitutions (1)
- Nanostructure; Metalloporphyrin; Poly(3 (1)
- ONIOM (1)
- QM/MM method (1)
- Quantum mechanical-molecular mechanics method (1)
- SNP arrays (1)
- Transmembrane and coiled-coil domains 1 gene (1)
- [Fe-Fe]-hydrogenase (1)
Articles 1 - 12 of 12
Full-Text Articles in Physical Sciences and Mathematics
[Fe-Fe]-Hydrogenase Reactivated By Residue Mutations As Bridging Carbonyl Rearranges: A Qm/Mm Study, Stefan Motiu, Valentin Gogonea
[Fe-Fe]-Hydrogenase Reactivated By Residue Mutations As Bridging Carbonyl Rearranges: A Qm/Mm Study, Stefan Motiu, Valentin Gogonea
Chemistry Faculty Publications
In this work, we found aqueous enzyme phase reaction pathways for the reactivation of the exogenously inhibited [Fe-Fe]-hydrogenases by O2, or OH−, which metabolizes to H2O (Dogaru et al., Int J Quantum Chem 2008, 108; Motiu et al., Int J Quantum Chem 2007, 107, 1248). We used the hybrid quantum mechanics/molecular mechanics (QM/MM) method to study the reactivation pathways of the exogenously inhibited enzyme matrix. The ONIOM calculations performed on the enzyme agree with experimental results (Liu et al., J Am Chem Soc 2002, 124, 5175), that is, wild-type [Fe-Fe]-hydrogenase H-cluster is inhibited by oxygen metabolites. An enzyme spherical region …
Dnmt1 Stability Is Regulated By Proteins Coordinating Deubiquitination And Acetylation-Driven Ubiquitination, Zhanwen Du, Jing Song, Yong Wang, Yiqing Zhao, Kishore Guda, Shuming Yang, Hung Ying Kao, Yan Xu, Joseph Willis, Sanford D. Markowitz, David Sedwick, Robert M. Ewing, Zhenghe Wang
Dnmt1 Stability Is Regulated By Proteins Coordinating Deubiquitination And Acetylation-Driven Ubiquitination, Zhanwen Du, Jing Song, Yong Wang, Yiqing Zhao, Kishore Guda, Shuming Yang, Hung Ying Kao, Yan Xu, Joseph Willis, Sanford D. Markowitz, David Sedwick, Robert M. Ewing, Zhenghe Wang
Chemistry Faculty Publications
DNA methyltransferase 1 (DNMT1) is the primary enzyme that maintains DNA methylation. We describe a previously unknown mode of regulation of DNMT1 protein stability through the coordinated action of an array of DNMT1-associated proteins. DNMT1 was destabilized by acetylation by the acetyltransferase Tip60, which triggered ubiquitination by the E3 ligase UHRF1, thereby targeting DNMT1 for proteasomal degradation. In contrast, DNMT1 was stabilized by histone deacetylase 1 (HDAC1) and the deubiquitinase HAUSP (herpes virus–associated ubiquitin-specific protease). Analysis of the abundance of DNMT1 and Tip60, as well as the association between HAUSP and DNMT1, suggested that during the cell cycle the initiation …
Cox-2 Inhibitor Nimesulide Analogs Are Aromatase Suppressors In Breast Cancer Cells, Bin Su, Xiaohan Cai, Yanyan Hong, Shiuan Chen
Cox-2 Inhibitor Nimesulide Analogs Are Aromatase Suppressors In Breast Cancer Cells, Bin Su, Xiaohan Cai, Yanyan Hong, Shiuan Chen
Chemistry Faculty Publications
Cyclooxygenase-2 (COX-2) inhibitor nimesulide derivatives compounds A and B decreased aromatase activity in breast cancer cells via a novel mechanism different to aromatase inhibitors (AIs), and were defined as “aromatase suppressors”. Breast carcinoma cells (MCF-7aro and T47Daro) transfected with aromatase full gene were used to explore the mechanisms of the two compounds. They dose and time-dependently suppressed aromatase activity in MCF-7aro and T47Daro cells in the nanomole range. However, they neither directly inhibited aromatase, nor improved aromatase degradation even at much higher concentrations. They could also suppress androgen stimulated cell growth, but did not affect estrogen enhanced cell proliferation. These …
Residue Mutations In [Fe-Fe]-Hydrogenase Impedes O 2 Binding: A Qm/Mm Investigation, Daniela Dogaru, Stefan Motiu, Valentin Gogonea
Residue Mutations In [Fe-Fe]-Hydrogenase Impedes O 2 Binding: A Qm/Mm Investigation, Daniela Dogaru, Stefan Motiu, Valentin Gogonea
Chemistry Faculty Publications
[Fe-Fe]-hydrogenases are enzymes that reversibly catalyze the reaction of protons and electrons to molecular hydrogen, which occurs in anaerobic media. In living systems, [Fe-Fe]-hydrogenases are mostly used for H(2) production. The [Fe-Fe]-hydrogenase H-cluster is the active site, which contains two iron atoms. The latest theoretical investigations1,2 advocate that the structure of di-iron air inhibited species are either Fe(p) (II)-Fe(d) (II)-O-H(-), or Fe(p) (II)-Fe(d) (II)-O-O-H, thus O(2) has to be prevented from binding to Fe(d) in all di-iron subcluster oxidation states in order to retain a catalytically active enzyme. By performing residue mutations on [Fe-Fe]-hydrogenases, we were able to weaken O(2) …
An Antimicrobial Peptide Regulates Tumor-Associated Macrophage Trafficking Via The Chemokine Receptor Ccr2, A Model For Tumorigenesis, Ge Jin, Hameem I. Kawsar, Stanley A. Hirsch, Chun Zeng, Xun Jia, Zhimin Feng, Santosh K. Ghosh, Qing Yin Zheng, Aimin Zhou, Thomas M. Mcintyre, Aaron Weinberg
An Antimicrobial Peptide Regulates Tumor-Associated Macrophage Trafficking Via The Chemokine Receptor Ccr2, A Model For Tumorigenesis, Ge Jin, Hameem I. Kawsar, Stanley A. Hirsch, Chun Zeng, Xun Jia, Zhimin Feng, Santosh K. Ghosh, Qing Yin Zheng, Aimin Zhou, Thomas M. Mcintyre, Aaron Weinberg
Chemistry Faculty Publications
Background: Tumor-associated macrophages (TAMs) constitute a significant part of infiltrating inflammatory cells that are frequently correlated with progression and poor prognosis of a variety of cancers. Tumor cell-produced human β-defensin-3 (hBD-3) has been associated with TAM trafficking in oral cancer; however, its involvement in tumor-related inflammatory processes remains largely unknown. Methodology: The relationship between hBD-3, monocyte chemoattractant protein-1 (MCP-1), TAMs, and CCR2 was examined using immunofluorescence microscopy in normal and oral carcinoma in situ biopsy specimens. The ability of hBD-3 to chemoattract host macrophages in vivo using a nude mouse model and analysis of hBD-3 on monocytic cell migration in …
Dna Polymerases: Perfect Enzymes For An Imperfect World, Anthony J. Berdis
Dna Polymerases: Perfect Enzymes For An Imperfect World, Anthony J. Berdis
Chemistry Faculty Publications
This Special Thematic Issue explores the molecular properties of DNA polymerases as extraordinary biological catalysts. In this short introductory chapter, I briefly highlight some of the most important concepts from the articles contained within this Special Issue. The contents of this Special Issue are arranged into distinct sub-categories corresponding to mechanistic studies of faithful DNA polymerization, studies of "specialized" DNA polymerases that function on damaged DNA, and DNA polymerases that are of therapeutic importance against various diseases. Emphasis is placed on understanding the dynamic cellular roles and biochemical functions of DNA polymerases, and how their structure and mechanism impact their …
Non-Natural Nucleotides As Probes For The Mechanism And Fidelity Of Dna Polymerases, Irene Lee, Anthony J. Berdis
Non-Natural Nucleotides As Probes For The Mechanism And Fidelity Of Dna Polymerases, Irene Lee, Anthony J. Berdis
Chemistry Faculty Publications
DNA is a remarkable macromolecule that functions primarily as the carrier of the genetic information of organisms ranging from viruses to bacteria to eukaryotes. The ability of DNA polymerases to efficiently and accurately replicate genetic material represents one of the most fundamental yet complex biological processes found in nature. The central dogma of DNA polymerization is that the efficiency and fidelity of this biological process is dependent upon proper hydrogen-bonding interactions between an incoming nucleotide and its templating partner. However, the foundation of this dogma has been recently challenged by the demonstration that DNA polymerases can effectively and, in some …
Terminal Deoxynucleotidyl Transferase: The Story Of A Misguided Dna Polymerase, Edward A. Motea, Anthony J. Berdis
Terminal Deoxynucleotidyl Transferase: The Story Of A Misguided Dna Polymerase, Edward A. Motea, Anthony J. Berdis
Chemistry Faculty Publications
Nearly every DNA polymerase characterized to date exclusively catalyzes the incorporation of mononucleotides into a growing primer using a DNA or RNA template as a guide to direct each incorporation event. There is, however, one unique DNA polymerase designated terminal deoxynucleotidyl transferase that performs DNA synthesis using only single-stranded DNA as the nucleic acid substrate. In this chapter, we review the biological role of this enigmatic DNA polymerase and the biochemical mechanism for its ability to perform DNA synthesis in the absence of a templating strand. We compare and contrast the molecular events for template-independent DNA synthesis catalyzed by terminal …
Nanostructured Poly(3,4-Ethylenedioxythiophene)–Metalloporphyrin Films: Improved Catalytic Detection Of Peroxynitrite, Serban Peteu, Pubudu Peiris, Ermias Gebermichael, Mekki Bayachou
Nanostructured Poly(3,4-Ethylenedioxythiophene)–Metalloporphyrin Films: Improved Catalytic Detection Of Peroxynitrite, Serban Peteu, Pubudu Peiris, Ermias Gebermichael, Mekki Bayachou
Chemistry Faculty Publications
We investigated in this paper the sensing performance of inherently conductive polymer, poly(3,4-ethylenedioxythiophene) (PEDOT), functionalized with hemin (iron protoporphyrin) as an electrocatalytic reporter. The sensing platform is prepared by electrodeposition of a composite film of hemin–PEDOT on a 30-μm diameter carbon fiber electrode (CFE). The polymerized films were characterized by field emission scanning electron microscopy (FESEM), which pointed to nanostructured films with tortuous pores. The electrocatalytic oxidation of peroxynitrite was characterized by cyclic voltammetry as well as other electrochemical methods. The catalytic current is proportional to the analyte's concentration. Optimized hemin–PEDOT modified CFEs were utilized for the first time to …
Selective Regulation Of Aromatase Expression For Drug Discovery, Robert W. Brueggemeier, Bin Su, Michael V. Darby, Yasuro Sugimoto
Selective Regulation Of Aromatase Expression For Drug Discovery, Robert W. Brueggemeier, Bin Su, Michael V. Darby, Yasuro Sugimoto
Chemistry Faculty Publications
Aromatase is a particularly attractive drug target in the treatment of hormone-responsive breast cancer, and aromatase activity in breast cancer patients is greater in or near the tumor tissue compared with the normal breast tissue. Complex regulation of aromatase expression in human tissues involves alternative promoter sites that provide tissue-specific control. Previous studies in our laboratories suggested a strong association between aromatase (CYP19) gene expression and the expression of cyclooxygenase (COX) genes. Additionally, COX selective inhibitors can suppress CYP19 gene expression and decrease aromatase activity. Our current hypothesis is that pharmacological regulation of aromatase can act locally to decrease the …
Homozygous Frameshift Mutation In Tmco1 Causes A Syndrome With Craniofacial Dysmorphism, Skeletal Anomalies, And Mental Retardation, Baozhong Xin, Erik G. Puffenberger, Susan Turben, Haiyan Tan, Aimin Zhou, Heng Wang
Homozygous Frameshift Mutation In Tmco1 Causes A Syndrome With Craniofacial Dysmorphism, Skeletal Anomalies, And Mental Retardation, Baozhong Xin, Erik G. Puffenberger, Susan Turben, Haiyan Tan, Aimin Zhou, Heng Wang
Chemistry Faculty Publications
We identified an autosomal recessive condition in 11 individuals in the Old Order Amish of northeastern Ohio. The syndrome was characterized by distinctive craniofacial dysmorphism, skeletal anomalies, and mental retardation. The typical craniofacial dysmorphism included brachycephaly, highly arched bushy eyebrows, synophrys, long eyelashes, low-set ears, microdontism of primary teeth, and generalized gingival hyperplasia, whereas Sprengel deformity of scapula, fusion of spine, rib abnormities, pectus excavatum, and pes planus represented skeletal anomalies. The genome-wide homozygosity mapping using six affected individuals localized the disease gene to a 3.3-Mb region on chromosome 1q23.3-q24.1. Candidate gene sequencing identified a homozygous frameshift mutation, c.139_140delAG, in …
Targeting Base Excision Repair Suggests A New Therapeutic Strategy Of Fludarabine For The Treatment Of Chronic Lymphocytic Leukemia, A. D. Bulgar, M. Snell, J. R. Donze, E. B. Kirkland, Lan Li, Shuming Yang, Yan Xu, S. L. Gerson, Lili Liu
Targeting Base Excision Repair Suggests A New Therapeutic Strategy Of Fludarabine For The Treatment Of Chronic Lymphocytic Leukemia, A. D. Bulgar, M. Snell, J. R. Donze, E. B. Kirkland, Lan Li, Shuming Yang, Yan Xu, S. L. Gerson, Lili Liu
Chemistry Faculty Publications
No abstract provided.