George A Papadantonakis | University of Illinois at Chicago (original) (raw)

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Papers by George A Papadantonakis

Research paper thumbnail of Ionization Patterns and Chemical Reactivity of Cytosine‐Guanine Watson‐Crick Pairs

ChemPhysChem, Mar 6, 2024

Research paper thumbnail of Electron and radical cation of sulfur-substituted thymine derivatives produced near photoionization threshold can alter and distort double-helix DNA structure

Chemical Physics Letters, Dec 1, 2019

Research paper thumbnail of A computational investigation of cytosine and 5-methyl cytosine reactivity by means of ionization potentials and one specific methylation pathway

Chemical Physics Letters, Aug 1, 2020

Results from DFT/ωB97X-D/6-311+G**/C-PCM calculations show that the aqueous vertical IP of 5-meth... more Results from DFT/ωB97X-D/6-311+G**/C-PCM calculations show that the aqueous vertical IP of 5-methylcytosine is lower than that of cytosine by 0.25 eV. Using the HSAB concept, the HOMO-LUMO gap for 5-methylcytosine is smaller than that of cytosine, making it soft and opt to form covalent bonds and more reactive. Carcinogenic methane diazonium ion can methylate cytosine at the N3 site and mutate it via an S N 2 mechanism and the activation energy is approximately 5.05 kcal/ mol in water. The rapid deamination of 5-methylcytosine results in thymine and

Research paper thumbnail of A theoretical investigation of the activation barriers for the N3-adenine methylation by carcinogenic methane diazonium ion

Computational and Theoretical Chemistry

Research paper thumbnail of Activation Barriers for Adenine Methylation by Methane Diazonium Ion and Dimethyl Sulfate

Biophysical Journal, Feb 1, 2021

Research paper thumbnail of Nanosecond UV laser photoionization of aqueous tryptophan: temperature dependence of quantum yield, mechanism, and kinetics of hydrated electron decay

Journal of Photochemistry and Photobiology A: Chemistry, 2000

The 266nm photoionization of aqueous tryptophan (Trp) solution at natural pH has been studied by ... more The 266nm photoionization of aqueous tryptophan (Trp) solution at natural pH has been studied by laser flash photolysis using 3–18mJ, 7ns, 266nm pulses. The transient absorption method was employed to detect hydrated electrons. The photoionization mechanism is a combination of mono and biphotonic processes. Results from measurements of the power dependence of photoionization and of triplet (T1) state production suggest

Research paper thumbnail of Activation barriers for methylation of DNA bases by dimethyl sulfate

Chemical Physics Letters, 2017

The S N 2 transition states of the methylation reaction of DNA bases with dimethyl sulfate were e... more The S N 2 transition states of the methylation reaction of DNA bases with dimethyl sulfate were examined employing DFT/ M06-2X/6-31+G ⁄ and DFT/B3LYP-D3/6-311+G (2df, 2p) levels of theory. Solvation effects were examined using the conductor-like polarizable continuum model (CPCM). Calculation results and feedback from electrostatic potential maps show that in water, charge separation lowers the activation barriers relative to the gas phase for the reactions at N7 of guanine, N3 of adenine and cytosine. Also, the reaction at the O 6 site of guanine is governed by steric interference and exhibits a higher activation barrier in water.

Research paper thumbnail of Conduction-band-edge ionization thresholds of DNA components in aqueous solution

Proceedings of the National Academy of Sciences, 1998

Research paper thumbnail of Spectral tuning in photoactive yellow protein by modulation of the shape of the excited state energy surface

Proceedings of the National Academy of Sciences, 2010

Research paper thumbnail of Activation Barriers for Adenine Methylation by Methane Diazonium Ion and Dimethyl Sulfate

Biophysical Journal, 2021

Research paper thumbnail of Side Chain Effect on Ir Spectra of Heterogeneous Peptide Sequence. Theoretical Investigation of a Series of Tripeptides (A-X-A)

Author Institution: Department of Chemistry, University of Illinois at Chicago, 845 West Taylor S... more Author Institution: Department of Chemistry, University of Illinois at Chicago, 845 West Taylor Street, Chicago 60607-7061 USA

Research paper thumbnail of High-throughput biophysics of functional tuning in photoactive yellow protein

Bulletin of the American Physical Society, 2007

Submitted for the MAR07 Meeting of The American Physical Society High-throughput biophysics of fu... more Submitted for the MAR07 Meeting of The American Physical Society High-throughput biophysics of functional tuning in photoactive yellow protein1 WOUTER HOFF, Dept of Microbiology and Molecular Genetics, Oklahoma State University, ANDREW PHILIP, GEORGE PAPADANTONAKIS, Dept of Biochemistry and Molecular Biology, University of Chicago, OSU TEAM, UOFC TEAM — The relationship between the structure of a protein and its function is a central unresolved problem in biology. We use photoactive yellow protein (PYP) to develop quantitative high-throughput methods to study this problem. PYP is a small bacterial photoreceptor with rhodopsin-like photochemistry based on its pcoumaric acid (pCA) chromophore. The absorbance maximum and pKa of the pCA in the active site of native PYP are shifted from 400 nm and 9.0 in water to 446 nm and 2.8 in the protein. Thus, PYP offers a unique model system to probe protein-ligand interactions. Here we show that high-throughput microscale methods can be used for ...

Research paper thumbnail of Author response for "In‐Silico Screening and Molecular Dynamics Simulation of Deleterious PAH Mutations Responsible for Phenylketonuria (PKU) Genetic Disorder

Research paper thumbnail of Functional tuning of photoactive yellow protein by active site residue 46

Protein-ligand interactions alter the properties of active site groups to achieve specific biolog... more Protein-ligand interactions alter the properties of active site groups to achieve specific biological functions. The active site of photoactive yellow protein (PYP) provides a model system for studying such functional tuning. PYP is a small bacterial photoreceptor with photochemistry based on its p-coumaric acid (pCA) chromophore. The absorbance maximum and pK(a) of the pCA in the active site of native PYP are shifted from 400 nm and 8.8 in water to 446 nm and 2.8 in the native protein milieu, respectively, by protein-ligand interactions. We report high-throughput microscale methods for the purification and spectroscopic investigation of PYP and use these to examine the role of active site residue Glu46 in PYP, which is hydrogen bonded to the pCA anion. The functional and structural attributes of the 19 substitution mutants of PYP at critical active site position 46 vary widely, with absorbance maxima from 441 to 478 nm, pCA fluorescence quantum yields from 0.19 to 1.4%, pCA pK(a) v...

Research paper thumbnail of Functional Tuning of Photoactive Yellow Protein by Active Site Residue 46†

Biochemistry, 2008

Protein−ligand interactions alter the properties of active site groups to achieve specific biolog... more Protein−ligand interactions alter the properties of active site groups to achieve specific biological functions. The active site of photoactive yellow protein (PYP) provides a model system for studying such functional tuning. PYP is a small bacterial photoreceptor with photochemistry based ...

Research paper thumbnail of Hydration effects on the photoionization energy of 2′-deoxyguanosine 5′-phosphate and activation barriers for guanine methylation by carcinogenic methane diazonium ions

Research paper thumbnail of Effects of Hydration on the Photoionization Threshold Energy of DNA Components and on the Activation Barriers for Guanine Methylation by Dimethyl Sulfate

Biophysical Journal, 2016

DNA of isolated nuclei from GM12878 cells under mild conditions of DNase I, yielding nicks in exp... more DNA of isolated nuclei from GM12878 cells under mild conditions of DNase I, yielding nicks in exposed areas of the chromatin. The nicks were subsequently labeled using red fluorescent-modified nucleotides. Next, long DNA molecules were extracted and a unique DNA barcode was formed using the BspQI nicking enzyme and green fluorescent-labeled nucleotides. The green-labeled barcode was used to align single long DNA molecules to a reference map and the red-labeled sites indicated the presence of DHS at specific positions. Comparison of our data with DNase I sequencing data from the ENCODE project showed a great agreement between the two methods. This method is easier to perform and can be done on new genomes with unknown sequences.

Research paper thumbnail of Evidence of temperature dependent activation barriers for near-threshold aqueous photoionization of 2 ′-deoxyguanosine and tryptophan

Chemical Physics Letters, 2001

Alkaline 2′-deoxyguanosine undergoes one- and two-photon laser photoionization at 266 nm. Similar... more Alkaline 2′-deoxyguanosine undergoes one- and two-photon laser photoionization at 266 nm. Similar to tryptophan and indole, the one-photon quantum yield increases five-fold between 296 and 362 K. Earlier Arrhenius analyses of tryptophan and indole photoionization rate constants, yielded unreasonably large pre-exponential factors (1013–1018s−1). An analysis employing pre-exponential factors for diffusion controlled reactions (1010–1011s−1) provides evidence of activation barriers that decrease

Research paper thumbnail of Spectral tuning in photoactive yellow protein by modulation of the shape of the excited state energy surface

Proceedings of the National Academy of Sciences

Protein-chromophore interactions in photoreceptors often shift the chromophore absorbance maximum... more Protein-chromophore interactions in photoreceptors often shift the chromophore absorbance maximum to a biologically relevant spectral region. A fundamental question regarding such spectral tuning effects is how the electronic ground state S(0) and excited state S(1) are modified by the protein. It is widely assumed that changes in energy gap between S(0) and S(1) are the main factor in biological spectral tuning. We report a generally applicable approach to determine if a specific residue modulates the energy gap, or if it alters the equilibrium nuclear geometry or width of the energy surfaces. This approach uses the effects that changes in these three parameters have on the absorbance and fluorescence emission spectra of mutants. We apply this strategy to a set of mutants of photoactive yellow protein (PYP) containing all 20 side chains at active site residue 46. While the mutants exhibit significant variation in both the position and width of their absorbance spectra, the fluoresc...

Research paper thumbnail of A computational investigation of cytosine and 5-methyl cytosine reactivity by means of ionization potentials and one specific methylation pathway

Research paper thumbnail of Ionization Patterns and Chemical Reactivity of Cytosine‐Guanine Watson‐Crick Pairs

ChemPhysChem, Mar 6, 2024

Research paper thumbnail of Electron and radical cation of sulfur-substituted thymine derivatives produced near photoionization threshold can alter and distort double-helix DNA structure

Chemical Physics Letters, Dec 1, 2019

Research paper thumbnail of A computational investigation of cytosine and 5-methyl cytosine reactivity by means of ionization potentials and one specific methylation pathway

Chemical Physics Letters, Aug 1, 2020

Results from DFT/ωB97X-D/6-311+G**/C-PCM calculations show that the aqueous vertical IP of 5-meth... more Results from DFT/ωB97X-D/6-311+G**/C-PCM calculations show that the aqueous vertical IP of 5-methylcytosine is lower than that of cytosine by 0.25 eV. Using the HSAB concept, the HOMO-LUMO gap for 5-methylcytosine is smaller than that of cytosine, making it soft and opt to form covalent bonds and more reactive. Carcinogenic methane diazonium ion can methylate cytosine at the N3 site and mutate it via an S N 2 mechanism and the activation energy is approximately 5.05 kcal/ mol in water. The rapid deamination of 5-methylcytosine results in thymine and

Research paper thumbnail of A theoretical investigation of the activation barriers for the N3-adenine methylation by carcinogenic methane diazonium ion

Computational and Theoretical Chemistry

Research paper thumbnail of Activation Barriers for Adenine Methylation by Methane Diazonium Ion and Dimethyl Sulfate

Biophysical Journal, Feb 1, 2021

Research paper thumbnail of Nanosecond UV laser photoionization of aqueous tryptophan: temperature dependence of quantum yield, mechanism, and kinetics of hydrated electron decay

Journal of Photochemistry and Photobiology A: Chemistry, 2000

The 266nm photoionization of aqueous tryptophan (Trp) solution at natural pH has been studied by ... more The 266nm photoionization of aqueous tryptophan (Trp) solution at natural pH has been studied by laser flash photolysis using 3–18mJ, 7ns, 266nm pulses. The transient absorption method was employed to detect hydrated electrons. The photoionization mechanism is a combination of mono and biphotonic processes. Results from measurements of the power dependence of photoionization and of triplet (T1) state production suggest

Research paper thumbnail of Activation barriers for methylation of DNA bases by dimethyl sulfate

Chemical Physics Letters, 2017

The S N 2 transition states of the methylation reaction of DNA bases with dimethyl sulfate were e... more The S N 2 transition states of the methylation reaction of DNA bases with dimethyl sulfate were examined employing DFT/ M06-2X/6-31+G ⁄ and DFT/B3LYP-D3/6-311+G (2df, 2p) levels of theory. Solvation effects were examined using the conductor-like polarizable continuum model (CPCM). Calculation results and feedback from electrostatic potential maps show that in water, charge separation lowers the activation barriers relative to the gas phase for the reactions at N7 of guanine, N3 of adenine and cytosine. Also, the reaction at the O 6 site of guanine is governed by steric interference and exhibits a higher activation barrier in water.

Research paper thumbnail of Conduction-band-edge ionization thresholds of DNA components in aqueous solution

Proceedings of the National Academy of Sciences, 1998

Research paper thumbnail of Spectral tuning in photoactive yellow protein by modulation of the shape of the excited state energy surface

Proceedings of the National Academy of Sciences, 2010

Research paper thumbnail of Activation Barriers for Adenine Methylation by Methane Diazonium Ion and Dimethyl Sulfate

Biophysical Journal, 2021

Research paper thumbnail of Side Chain Effect on Ir Spectra of Heterogeneous Peptide Sequence. Theoretical Investigation of a Series of Tripeptides (A-X-A)

Author Institution: Department of Chemistry, University of Illinois at Chicago, 845 West Taylor S... more Author Institution: Department of Chemistry, University of Illinois at Chicago, 845 West Taylor Street, Chicago 60607-7061 USA

Research paper thumbnail of High-throughput biophysics of functional tuning in photoactive yellow protein

Bulletin of the American Physical Society, 2007

Submitted for the MAR07 Meeting of The American Physical Society High-throughput biophysics of fu... more Submitted for the MAR07 Meeting of The American Physical Society High-throughput biophysics of functional tuning in photoactive yellow protein1 WOUTER HOFF, Dept of Microbiology and Molecular Genetics, Oklahoma State University, ANDREW PHILIP, GEORGE PAPADANTONAKIS, Dept of Biochemistry and Molecular Biology, University of Chicago, OSU TEAM, UOFC TEAM — The relationship between the structure of a protein and its function is a central unresolved problem in biology. We use photoactive yellow protein (PYP) to develop quantitative high-throughput methods to study this problem. PYP is a small bacterial photoreceptor with rhodopsin-like photochemistry based on its pcoumaric acid (pCA) chromophore. The absorbance maximum and pKa of the pCA in the active site of native PYP are shifted from 400 nm and 9.0 in water to 446 nm and 2.8 in the protein. Thus, PYP offers a unique model system to probe protein-ligand interactions. Here we show that high-throughput microscale methods can be used for ...

Research paper thumbnail of Author response for "In‐Silico Screening and Molecular Dynamics Simulation of Deleterious PAH Mutations Responsible for Phenylketonuria (PKU) Genetic Disorder

Research paper thumbnail of Functional tuning of photoactive yellow protein by active site residue 46

Protein-ligand interactions alter the properties of active site groups to achieve specific biolog... more Protein-ligand interactions alter the properties of active site groups to achieve specific biological functions. The active site of photoactive yellow protein (PYP) provides a model system for studying such functional tuning. PYP is a small bacterial photoreceptor with photochemistry based on its p-coumaric acid (pCA) chromophore. The absorbance maximum and pK(a) of the pCA in the active site of native PYP are shifted from 400 nm and 8.8 in water to 446 nm and 2.8 in the native protein milieu, respectively, by protein-ligand interactions. We report high-throughput microscale methods for the purification and spectroscopic investigation of PYP and use these to examine the role of active site residue Glu46 in PYP, which is hydrogen bonded to the pCA anion. The functional and structural attributes of the 19 substitution mutants of PYP at critical active site position 46 vary widely, with absorbance maxima from 441 to 478 nm, pCA fluorescence quantum yields from 0.19 to 1.4%, pCA pK(a) v...

Research paper thumbnail of Functional Tuning of Photoactive Yellow Protein by Active Site Residue 46†

Biochemistry, 2008

Protein−ligand interactions alter the properties of active site groups to achieve specific biolog... more Protein−ligand interactions alter the properties of active site groups to achieve specific biological functions. The active site of photoactive yellow protein (PYP) provides a model system for studying such functional tuning. PYP is a small bacterial photoreceptor with photochemistry based ...

Research paper thumbnail of Hydration effects on the photoionization energy of 2′-deoxyguanosine 5′-phosphate and activation barriers for guanine methylation by carcinogenic methane diazonium ions

Research paper thumbnail of Effects of Hydration on the Photoionization Threshold Energy of DNA Components and on the Activation Barriers for Guanine Methylation by Dimethyl Sulfate

Biophysical Journal, 2016

DNA of isolated nuclei from GM12878 cells under mild conditions of DNase I, yielding nicks in exp... more DNA of isolated nuclei from GM12878 cells under mild conditions of DNase I, yielding nicks in exposed areas of the chromatin. The nicks were subsequently labeled using red fluorescent-modified nucleotides. Next, long DNA molecules were extracted and a unique DNA barcode was formed using the BspQI nicking enzyme and green fluorescent-labeled nucleotides. The green-labeled barcode was used to align single long DNA molecules to a reference map and the red-labeled sites indicated the presence of DHS at specific positions. Comparison of our data with DNase I sequencing data from the ENCODE project showed a great agreement between the two methods. This method is easier to perform and can be done on new genomes with unknown sequences.

Research paper thumbnail of Evidence of temperature dependent activation barriers for near-threshold aqueous photoionization of 2 ′-deoxyguanosine and tryptophan

Chemical Physics Letters, 2001

Alkaline 2′-deoxyguanosine undergoes one- and two-photon laser photoionization at 266 nm. Similar... more Alkaline 2′-deoxyguanosine undergoes one- and two-photon laser photoionization at 266 nm. Similar to tryptophan and indole, the one-photon quantum yield increases five-fold between 296 and 362 K. Earlier Arrhenius analyses of tryptophan and indole photoionization rate constants, yielded unreasonably large pre-exponential factors (1013–1018s−1). An analysis employing pre-exponential factors for diffusion controlled reactions (1010–1011s−1) provides evidence of activation barriers that decrease

Research paper thumbnail of Spectral tuning in photoactive yellow protein by modulation of the shape of the excited state energy surface

Proceedings of the National Academy of Sciences

Protein-chromophore interactions in photoreceptors often shift the chromophore absorbance maximum... more Protein-chromophore interactions in photoreceptors often shift the chromophore absorbance maximum to a biologically relevant spectral region. A fundamental question regarding such spectral tuning effects is how the electronic ground state S(0) and excited state S(1) are modified by the protein. It is widely assumed that changes in energy gap between S(0) and S(1) are the main factor in biological spectral tuning. We report a generally applicable approach to determine if a specific residue modulates the energy gap, or if it alters the equilibrium nuclear geometry or width of the energy surfaces. This approach uses the effects that changes in these three parameters have on the absorbance and fluorescence emission spectra of mutants. We apply this strategy to a set of mutants of photoactive yellow protein (PYP) containing all 20 side chains at active site residue 46. While the mutants exhibit significant variation in both the position and width of their absorbance spectra, the fluoresc...

Research paper thumbnail of A computational investigation of cytosine and 5-methyl cytosine reactivity by means of ionization potentials and one specific methylation pathway