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3 Methyladenine

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James T Stivers – 1st expert on this subject based on the ideXlab platform

  • solution structure and base perturbation studies reveal a novel mode of alkylated base recognition by 3 Methyladenine dna glycosylase i
    Journal of Biological Chemistry, 2003
    Co-Authors: Keehwan Kwon, Alexander C Drohat, Yu Lin Jiang, James T Stivers

    Abstract:

    Abstract The specific recognition mechanisms of DNA repair glycosylases that remove cationic alkylpurine bases in DNA are not well understood partly due to the absence of structures of these enzymes with their cognate bases. Here we report the solution structure of 3Methyladenine DNA glycosylase I (TAG) in complex with its 3Methyladenine (3-MeA) cognate base, and we have used chemical perturbation of the base in combination with mutagenesis of the enzyme to evaluate the role of hydrogen bonding and π-cation interactions in alkylated base recognition by this DNA repair enzyme. We find that TAG uses hydrogen bonding with heteroatoms on the base, van der Waals interactions with the 3-Me group, and conventional π-π stacking with a conserved Trp side chain to selectively bind neutral 3-MeA over the cationic form of the base. Discrimination against binding of the normal base adenine is derived from direct sensing of the 3-methyl group, leading to an induced-fit conformational change that engulfs the base in a box defined by five aromatic side chains. These findings indicate that base specific recognition by TAG does not involve strong π-cation interactions, and suggest a novel mechanism for alkylated base recognition and removal.

  • a novel zinc snap motif conveys structural stability to 3 Methyladenine dna glycosylase i
    Journal of Biological Chemistry, 2003
    Co-Authors: Keehwan Kwon, James T Stivers

    Abstract:

    Abstract The Escherichia coli 3Methyladenine DNA glycosylase I (TAG) is a DNA repair enzyme that excises 3Methyladenine in DNA and is the smallest member of the helix-hairpin-helix (HhH) superfamily of DNA glycosylases. Despite many studies over the last 25 years, there has been no suggestion that TAG was a metalloprotein. However, here we establish by heteronuclear NMR and other spectroscopic methods that TAG binds 1 eq of Zn2+ extremely tightly. A family of refined NMR structures shows that 4 conserved residues contributed from the amino- and carboxyl-terminal regions of TAG (Cys4, His17, His175, and Cys179) form a Zn2+ binding site. The Zn2+ ion serves to tether the otherwise unstructured amino- and carboxyl-terminal regions of TAG. We propose that this unexpected “zinc snap” motif in the TAG family (CX12–17HX∼150HX3C) serves to stabilize the HhH domain thereby mimicking the functional role of protein-protein interactions in larger HhH superfamily members.

  • A novel zinc snap motif conveys structural stability to 3Methyladenine DNA glycosylase I
    Journal of Biological Chemistry, 2003
    Co-Authors: Keehwan Kwon, Chunyang Cao, James T Stivers

    Abstract:

    The Escherichia coli 3Methyladenine DNA glycosylase I (TAG) is a DNA repair enzyme that excises 3Methyladenine in DNA and is the smallest member of the helix-hairpin-helix (HhH) superfamily of DNA glycosylases. Despite many studies over the last 25 years, there has been no suggestion that TAG was a metalloprotein. However, here we establish by heteronuclear NMR and other spectroscopic methods that TAG binds 1 eq of Zn2+ extremely tightly. A family of refined NMR structures shows that 4 conserved residues contributed from the amino- and carboxyl-terminal regions of TAG (Cys4, His17, His175, and Cys179) form a Zn2+ binding site. The Zn2+ ion serves to tether the otherwise unstructured amino- and carboxyl-terminal regions of TAG. We propose that this unexpected “zinc snap” motif in the TAG family (CX(12-17)HX(approximately 150)HX(3)C) serves to stabilize the HhH domain thereby mimicking the functional role of protein-protein interactions in larger HhH superfamily members.

Keehwan Kwon – 2nd expert on this subject based on the ideXlab platform

  • solution structure and base perturbation studies reveal a novel mode of alkylated base recognition by 3 Methyladenine dna glycosylase i
    Journal of Biological Chemistry, 2003
    Co-Authors: Keehwan Kwon, Alexander C Drohat, Yu Lin Jiang, James T Stivers

    Abstract:

    Abstract The specific recognition mechanisms of DNA repair glycosylases that remove cationic alkylpurine bases in DNA are not well understood partly due to the absence of structures of these enzymes with their cognate bases. Here we report the solution structure of 3Methyladenine DNA glycosylase I (TAG) in complex with its 3Methyladenine (3-MeA) cognate base, and we have used chemical perturbation of the base in combination with mutagenesis of the enzyme to evaluate the role of hydrogen bonding and π-cation interactions in alkylated base recognition by this DNA repair enzyme. We find that TAG uses hydrogen bonding with heteroatoms on the base, van der Waals interactions with the 3-Me group, and conventional π-π stacking with a conserved Trp side chain to selectively bind neutral 3-MeA over the cationic form of the base. Discrimination against binding of the normal base adenine is derived from direct sensing of the 3-methyl group, leading to an induced-fit conformational change that engulfs the base in a box defined by five aromatic side chains. These findings indicate that base specific recognition by TAG does not involve strong π-cation interactions, and suggest a novel mechanism for alkylated base recognition and removal.

  • a novel zinc snap motif conveys structural stability to 3 Methyladenine dna glycosylase i
    Journal of Biological Chemistry, 2003
    Co-Authors: Keehwan Kwon, James T Stivers

    Abstract:

    Abstract The Escherichia coli 3Methyladenine DNA glycosylase I (TAG) is a DNA repair enzyme that excises 3Methyladenine in DNA and is the smallest member of the helix-hairpin-helix (HhH) superfamily of DNA glycosylases. Despite many studies over the last 25 years, there has been no suggestion that TAG was a metalloprotein. However, here we establish by heteronuclear NMR and other spectroscopic methods that TAG binds 1 eq of Zn2+ extremely tightly. A family of refined NMR structures shows that 4 conserved residues contributed from the amino- and carboxyl-terminal regions of TAG (Cys4, His17, His175, and Cys179) form a Zn2+ binding site. The Zn2+ ion serves to tether the otherwise unstructured amino- and carboxyl-terminal regions of TAG. We propose that this unexpected “zinc snap” motif in the TAG family (CX12–17HX∼150HX3C) serves to stabilize the HhH domain thereby mimicking the functional role of protein-protein interactions in larger HhH superfamily members.

  • A novel zinc snap motif conveys structural stability to 3Methyladenine DNA glycosylase I
    Journal of Biological Chemistry, 2003
    Co-Authors: Keehwan Kwon, Chunyang Cao, James T Stivers

    Abstract:

    The Escherichia coli 3Methyladenine DNA glycosylase I (TAG) is a DNA repair enzyme that excises 3Methyladenine in DNA and is the smallest member of the helix-hairpin-helix (HhH) superfamily of DNA glycosylases. Despite many studies over the last 25 years, there has been no suggestion that TAG was a metalloprotein. However, here we establish by heteronuclear NMR and other spectroscopic methods that TAG binds 1 eq of Zn2+ extremely tightly. A family of refined NMR structures shows that 4 conserved residues contributed from the amino- and carboxyl-terminal regions of TAG (Cys4, His17, His175, and Cys179) form a Zn2+ binding site. The Zn2+ ion serves to tether the otherwise unstructured amino- and carboxyl-terminal regions of TAG. We propose that this unexpected “zinc snap” motif in the TAG family (CX(12-17)HX(approximately 150)HX(3)C) serves to stabilize the HhH domain thereby mimicking the functional role of protein-protein interactions in larger HhH superfamily members.

Shabbir Ahmad – 3rd expert on this subject based on the ideXlab platform

  • quantum chemical and spectroscopic investigations of 3 Methyladenine
    Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 2014
    Co-Authors: Mohammad Jane Alam, Shabbir Ahmad

    Abstract:

    Abstract FTIR, FT-Raman and UV–Vis spectra of 3Methyladenine have been recorded and investigated using quantum chemical calculations. The molecular geometry and vibrational spectra of 3Methyladenine in the ground state are computed by using HF and DFT methods with 6-311G(d,p) basis set. VSCF, CC-VSCF methods based on 2MR-QFF and PT2 (Barone method) have been utilized for computing anharmonic vibrational frequencies. These methods yield results that are in remarkable agreement with the experimental data. The magnitudes of coupling between pair of modes have been also computed. Vibrational modes are assigned with the help of visual inspection of atomic displacements. The electronic spectra, simulated at TD-B3LYP/6-311++G(d,p) level of theory, are compared to the experiment. The global quantities: electronic chemical potential, electrophilicity index, chemical hardness and softness based on HOMO and LUMO energy eigenvalues are also computed at B3LYP/6-311++G(d,p) level of theory.

  • Quantum chemical and spectroscopic investigations of 3Methyladenine
    Spectrochimica Acta – Part A: Molecular and Biomolecular Spectroscopy, 2014
    Co-Authors: Mohammad Jane Alam, Shabbir Ahmad

    Abstract:

    FTIR, FT-Raman and UV-Vis spectra of 3Methyladenine have been recorded and investigated using quantum chemical calculations. The molecular geometry and vibrational spectra of 3Methyladenine in the ground state are computed by using HF and DFT methods with 6-311G(d,p) basis set. VSCF, CC-VSCF methods based on 2MR-QFF and PT2 (Barone method) have been utilized for computing anharmonic vibrational frequencies. These methods yield results that are in remarkable agreement with the experimental data. The magnitudes of coupling between pair of modes have been also computed. Vibrational modes are assigned with the help of visual inspection of atomic displacements. The electronic spectra, simulated at TD-B3LYP/6-311++G(d,p) level of theory, are compared to the experiment. The global quantities: electronic chemical potential, electrophilicity index, chemical hardness and softness based on HOMO and LUMO energy eigenvalues are also computed at B3LYP/6-311++G(d,p) level of theory. ?? 2014 Elsevier B.V. All rights reserved.