Khiem Van Nguyen
University of Utah
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Publication
Featured researches published by Khiem Van Nguyen.
Journal of Biological Chemistry | 2009
Xylophone V. Victor; Thao Kim Nu Nguyen; Manivannan Ethirajan; Vy M. Tran; Khiem Van Nguyen; Balagurunathan Kuberan
Glycosaminoglycan (GAG) biosynthesis requires numerous biosynthetic enzymes and activated sulfate and sugar donors. Although the sequence of biosynthetic events is resolved using reconstituted systems, little is known about the emergence of cell-specific GAG chains (heparan sulfate, chondroitin sulfate, and dermatan sulfate) with distinct sulfation patterns. We have utilized a library of click-xylosides that have various aglycones to decipher the mechanism of GAG biosynthesis in a cellular system. Earlier studies have shown that both the concentration of the primers and the structure of the aglycone moieties can affect the composition of the newly synthesized GAG chains. However, it is largely unknown whether structural features of aglycone affect the extent of sulfation, sulfation pattern, disaccharide composition, and chain length of GAG chains. In this study, we show that aglycones can switch not only the type of GAG chains, but also their fine structures. Our findings provide suggestive evidence for the presence of GAGOSOMES that have different combinations of enzymes and their isoforms regulating the synthesis of cell-specific combinatorial structures. We surmise that click-xylosides are differentially recognized by the GAGOSOMES to generate distinct GAG structures as observed in this study. These novel click-xylosides offer new avenues to profile the cell-specific GAG chains, elucidate the mechanism of GAG biosynthesis, and to decipher the biological actions of GAG chains in model organisms.
Proceedings of the National Academy of Sciences of the United States of America | 2014
Yuyuan Zhang; Jordan Dood; Ashley A. Beckstead; Xi Bo Li; Khiem Van Nguyen; Cynthia J. Burrows; Roberto Improta; Bern Kohler
Significance UV photons are absorbed strongly by DNA, but rarely cause permanent photodamage. Single nucleobases are protected by ultrafast nonradiative decay, but excited states in single- and double-stranded DNA decay very differently. An intensely debated question is whether a UV photon can move an electron from one nucleobase to another along a single strand. This study demonstrates that UV absorption efficiently transfers an electron from an oxidatively damaged guanine (8-oxo-G) to adenine in a dinucleotide mimic of the flavin cofactor FADH2, yielding radicals that decay in 60 ps. It is proposed that the photoredox activity of 8-oxo-G, which may have repaired cyclobutane pyrimidine dimers in the RNA world, reflects the importance of ultrafast charge separation between stacked nucleobases by UV radiation. During the early evolution of life, 8-oxo-7,8-dihydro-2′-deoxyguanosine (O) may have functioned as a proto-flavin capable of repairing cyclobutane pyrimidine dimers in DNA or RNA by photoinduced electron transfer using longer wavelength UVB radiation. To investigate the ability of O to act as an excited-state electron donor, a dinucleotide mimic of the FADH2 cofactor containing O at the 5′-end and 2′-deoxyadenosine at the 3′-end was studied by femtosecond transient absorption spectroscopy in aqueous solution. Following excitation with a UV pulse, a broadband mid-IR pulse probed vibrational modes of ground-state and electronically excited molecules in the double-bond stretching region. Global analysis of time- and frequency-resolved transient absorption data coupled with ab initio quantum mechanical calculations reveal vibrational marker bands of nucleobase radical ions formed by electron transfer from O to 2′-deoxyadenosine. The quantum yield of charge separation is 0.4 at 265 nm, but decreases to 0.1 at 295 nm. Charge recombination occurs in 60 ps before the O radical cation can lose a deuteron to water. Kinetic and thermodynamic considerations strongly suggest that all nucleobases can undergo ultrafast charge separation when π-stacked in DNA or RNA. Interbase charge transfer is proposed to be a major decay pathway for UV excited states of nucleic acids of great importance for photostability as well as photoredox activity.
ChemBioChem | 2008
Balagurunathan Kuberan; Manivannan Ethirajan; Xylophone V. Victor; Vy M. Tran; Khiem Van Nguyen; Anh Do
Proteoglycans are composed of a core protein and several complex glycosaminoglycan (GAG) polysaccharide side chains. Heparan sulfate (HS), chondroitin sulfate (CS) and dermatan sulfate (DS) belong to the family of GAGs. In humans, these GAG side chains have been shown to regulate many biological functions, including wound healing, cell signaling, cell differentiation, angiogenesis, blood clotting, and tumor-cell migration. GAGs consist of repeating disaccharide units of hexosamine and uronic acid, and are covalently ACHTUNGTRENNUNGattached to a serine residue of the core protein via a specific linkage tetrasaccharide (Figure 1). The very first step in GAG synthesis is xylosylation of a serine residue of the core protein, followed by assembly of a tetrasaccharide unit that serves as an acceptor for elongation of GAG chains.
SPR Electrochemistry | 2015
David P. Hickey; Ross D. Milton; Michelle Rasmussen; Sofiene Abdellaoui; Khiem Van Nguyen; Shelley D. Minteer
This book chapter will detail the fundamentals of direct and mediated bioelectrocatalysis, as well as the applications of bioelectrocatalysis. Applications discussed include environmental, biomedical, and food and drink biosensors, self-powered sensors, biofuel cells, biosolar cells, and bioelectrosynthesis of value added products.
Journal of the American Chemical Society | 2011
Khiem Van Nguyen; Cynthia J. Burrows
Chemical Communications | 2015
Khiem Van Nguyen; Shelley D. Minteer
Accounts of Chemical Research | 2012
Khiem Van Nguyen; Cynthia J. Burrows
Journal of The Electrochemical Society | 2014
Khiem Van Nguyen; Fabien Giroud; Shelley D. Minteer
Journal of Physical Chemistry B | 2015
Yuyuan Zhang; Jordan Dood; Ashley A. Beckstead; Xi Bo Li; Khiem Van Nguyen; Cynthia J. Burrows; Roberto Improta; Bern Kohler
ACS Catalysis | 2016
Khiem Van Nguyen; Yaovi Holade; Shelley D. Minteer