The adenine ring influences the adenosine 5′-triphosphate hydrolysis

In this work, we report the cocrystallization of N9-ethyladenine with 1,2,4,5-tetrafluoro-3,6-diiodobenzene (TFDIB), a classical XB donor. As far as our knowledge extends, this is the first cocrystal reported to date where an adenine derivative acts as a halogen bond acceptor. In the solid state, each adenine ring forms two centrosymmetric H-bonded dimers: one using N1···HA6–N6 and the other N7···HB6–N6. Therefore, only N3 is available as a halogen bond acceptor that, indeed, establishes an N···I halogen bonding interaction with TFDIB. The H-bonded dimers and halogen bonds have been investigated via DFT (Density Functional Theory) calculations and the Bader’s Quantum Theory of Atoms In Molecules (QTAIM) method at the B3LYP/6-311+G* level of theory. The influence of H-bonding interactions on the lone pair donor ability of N3 has also been analyzed using the molecular electrostatic potential (MEP) surface calculations.

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Photoaffinity labelling of human poly(ADP-ribose) polymerase catalytic domain

Biochemical Journal ◽

10.1042/bj3220469 ◽

1997 ◽

Vol 322 (2) ◽

pp. 469-475 ◽

Cited By ~ 12

Author(s):

Hyuntae KIM ◽

Myron K. JACOBSON ◽

Véronique ROLLI ◽

Josiane MÉNISSIER-de MURCIA ◽

Joseph REINBOLT ◽

...

Keyword(s):

Catalytic Domain ◽

Insertion Site ◽

Site Directed Mutagenesis ◽

Crystallographic Structure ◽

Reverse Phase Hplc ◽

Reverse Phase ◽

Photoaffinity Labelling ◽

Adenine Ring ◽

Boronate Affinity Chromatography ◽

Binding Residues

Photoaffinity labelling of the human poly(ADP-ribose) polymerase (PARP) catalytic domain (40 kDa) with the NAD+ photoaffinity analogue 2-azido-[α-32P]NAD+ has been used to identify NAD+-binding residues. In the presence of UV, photoinsertion of the analogue was observed with a stoichiometry of 0.73 mol of 2-azido-[α-32P]NAD+ per mol of catalytic domain. Competition experiments indicated that 3-aminobenzamide strongly protected the insertion site. Residues binding the adenine ring of NAD+ were identified by trypsin digestion and boronate affinity chromatography in combination with reverse-phase HPLC. Two major NAD+-binding residues, Trp1014 of peptide Thr1011–Trp1014 and Lys893 of peptide Ile879 –Lys893, were identified. The site-directed mutagenesis of these two residues revealed that Lys893, but not Trp1014, is critical for activity. The close positioning of Lys893 near the adenine ring of NAD+ has been confirmed by the recently solved crystallographic structure of the chicken PARP catalytic domain [Ruf, Ménissier-de Murcia, de Murcia and Schulz (1996) Proc. Natl. Acad. Sci. U.S.A. 93, 7481–7485].

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The Effects Of Derivatives Of Adenosine 3',5'-Monophosphate On Fluid Secretion By The Salivary Glands Of Calliphora

Journal of Experimental Biology ◽

10.1242/jeb.59.3.595 ◽

1973 ◽

Vol 59 (3) ◽

pp. 595-606

Author(s):

M. J. BERRIDGE

Keyword(s):

Cyclic Amp ◽

Salivary Glands ◽

Cyclic Nucleotides ◽

Fluid Secretion ◽

Receptor Interaction ◽

Base Region ◽

Adenine Ring ◽

Derivatives Of ◽

Ribose Sugar

1. The nature of the cyclic AMP-receptor interaction was analysed by testing a range of cyclic nucleotides on the isolated salivary glands of adult blowflies. 2. All compounds containing modifications in the region of ribose or the phosphate ring were inactive. One compound, adenosine 3',5'-phosphorothioate, appeared to compete with cyclic AMP. 3. A number of nucleotides with alterations restricted to the base region of the molecule could stimulate secretion equally as well as cyclic AMP. 4. These observations indicate that during the action of cyclic AMP the phosphate ring and ribose sugar are critical whereas the adenine ring plays a relatively unspecific role.

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P219L substitution in human D-amino acid oxidase impacts the ligand binding and catalytic efficiency

The Journal of Biochemistry ◽

10.1093/jb/mvaa083 ◽

2020 ◽

Vol 168 (5) ◽

pp. 557-567

Author(s):

Wanitcha Rachadech ◽

Yusuke Kato ◽

Rabab M Abou El-Magd ◽

Yuji Shishido ◽

Soo Hyeon Kim ◽

...

Keyword(s):

Amino Acid ◽

Conformational Changes ◽

Active Site ◽

Structural Changes ◽

Catalytic Efficiency ◽

Acid Oxidase ◽

Wild Type ◽

Amino Acid Oxidase ◽

Adenine Ring ◽

The Impact

Abstract Human D-amino acid oxidase (DAO) is a flavoenzyme that is implicated in neurodegenerative diseases. We investigated the impact of replacement of proline with leucine at Position 219 (P219L) in the active site lid of human DAO on the structural and enzymatic properties, because porcine DAO contains leucine at the corresponding position. The turnover numbers (kcat) of P219L were unchanged, but its Km values decreased compared with wild-type, leading to an increase in the catalytic efficiency (kcat/Km). Moreover, benzoate inhibits P219L with lower Ki value (0.7–0.9 µM) compared with wild-type (1.2–2.0 µM). Crystal structure of P219L in complex with flavin adenine dinucleotide (FAD) and benzoate at 2.25 Å resolution displayed conformational changes of the active site and lid. The distances between the H-bond-forming atoms of arginine 283 and benzoate and the relative position between the aromatic rings of tyrosine 224 and benzoate were changed in the P219L complex. Taken together, the P219L substitution leads to an increase in the catalytic efficiency and binding affinity for substrates/inhibitors due to these structural changes. Furthermore, an acetic acid was located near the adenine ring of FAD in the P219L complex. This study provides new insights into the structure–function relationship of human DAO.

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ChemInform Abstract: SYNTHESIS OF 7,9-DISUBSTITUTED ADENINES, THE USE OF THE METHOXYL GROUP AS A DIRECTING GROUP IN N-ALKYLATION OF THE ADENINE RING

Chemischer Informationsdienst ◽

10.1002/chin.197411372 ◽

1974 ◽

Vol 5 (11) ◽

pp. no-no

Author(s):

T. FUJII ◽

F. TANAKA ◽

K. MOHRI ◽

T. ITAYA ◽

T. SAITO

Keyword(s):

Methoxyl Group ◽

Adenine Ring ◽

Directing Group

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Calculation of the Geometries and Infrared Spectra of the Stacked Cofactor Flavin Adenine Dinucleotide (FAD) as the Prerequisite for Studies of Light-Triggered Proton and Electron Transfer

Biomolecules ◽

10.3390/biom10040573 ◽

2020 ◽

Vol 10 (4) ◽

pp. 573

Author(s):

Martina Kieninger ◽

Oscar N. Ventura ◽

Tilman Kottke

Keyword(s):

Infrared Spectra ◽

Density Functional ◽

Flavin Adenine Dinucleotide ◽

Hydroxyl Group ◽

Flavin Mononucleotide ◽

Experimental Investigations ◽

Adenine Ring ◽

Π Complex ◽

Wide Range ◽

Single Water Molecule

Flavin cofactors, like flavin adenine dinucleotide (FAD), are important electron shuttles in living systems. They catalyze a wide range of one- or two-electron redox reactions. Experimental investigations include UV-vis as well as infrared spectroscopy. FAD in aqueous solution exhibits a significantly shorter excited state lifetime than its analog, the flavin mononucleotide. This finding is explained by the presence of a “stacked” FAD conformation, in which isoalloxazine and adenine moieties form a π-complex. Stacking of the isoalloxazine and adenine rings should have an influence on the frequency of the vibrational modes. Density functional theory (DFT) studies of the closed form of FAD in microsolvation (explicit water) were used to reproduce the experimental infrared spectra, substantiating the prevalence of the stacked geometry of FAD in aqueous surroundings. It could be shown that the existence of the closed structure in FAD can be narrowed down to the presence of only a single water molecule between the third hydroxyl group (of the ribityl chain) and the N7 in the adenine ring of FAD.

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Spectroelectrochemical Investigation of the Interaction of Adenine with Pyridoxine at Physiological pH

Journal of Spectroscopy ◽

10.1155/2019/6979547 ◽

2019 ◽

Vol 2019 ◽

pp. 1-12

Author(s):

Yasmin Roye ◽

Uche Udeochu ◽

Maraizu Ukaegbu ◽

Jonathan Onuegbu

Keyword(s):

Raman Band ◽

Bathochromic Shift ◽

Surface Enhanced Raman Spectroscopy ◽

Raman Shift ◽

Sers Spectrum ◽

Visible Absorption ◽

Adenine Ring ◽

Surface Enhanced ◽

Surface Enhanced Raman ◽

The Individual

Spectroelectrochemical techniques were used to probe the interaction of adenine with pyridoxine at pH 7.0. Analysis of UV-visible absorption of the adenine-pyridoxine complex at 260 nm using the Lineweaver–Burk double reciprocal plot produced a linear graph indicating a 1 : 1 mode of interaction between the compounds and a binding constant of 29.1. Change in the background current and broadening of adenine and pyridoxine cyclic voltammetry (CV) oxidation peaks at 1.0 V and 0.8 V, respectively, compared to the CV of the individual compounds is indicative of an interaction. The Raman shift of the coupled –C(11)H2-OH bending and in-plane N(7)-H mode at 1235 cm−1 to 1215 cm−1 of pyridoxine and the shift to the lower wavenumber of the adenine –N(10)H2 rocking band from 942 to 906 cm−1 confirm that the adenine exocyclic amino group and its purine nitrogen atom N(7) interacts with pyridoxine O(12) via the formation of hydrogen bonds. Strong enhancement of surface-enhanced Raman spectroscopy (SERS) bands pertaining to adenine and the bathochromic shift of the normal Raman band due to the adenine ring breathing mode observed at 722 cm−1 in the spectrum of adenine, to 732 cm−1 in the SERS spectrum of aqueous adenine-pyridoxine indicates that the complex adsorbs onto the Ag nanoparticle surface with the adenine portion possessing a perpendicular orientation.

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