Characterization and elucidation of coordination requirements of adenine nucleotides complexes with Fe(II) ions.
In spite of the significant role of iron ions-nucleotide complexes in living cells, these complexes have been studied only to a limited extent. Therefore, we fully characterized the ATP:Fe(II) complex including stoichiometry, geometry, stability constants, and dependence of Fe(II)-coordination on pH. A 1:1 stoichiometry was established for the ATP:Fe(II) complex based on volumetric titrations, UV and SEM/EDX measurements. The coordination sites of ferrous ions in the complex with ATP, established by 1H-, 31P-, and 15N-NMR, involve the adenine N7 as well as P(alpha), P(beta), and P(gamma). Coordination sites remain the same within the pH range of 3.1-8.3. By applying fluorescence monitored Fe(II)-titration, we established a logK value of 5.13 for the Fe(ATP)2- complex, and 2.31 for the Fe(HATP)-complex. Ferrous complexes of ADP3- and AMP2- were less stable (log K 4.43 and 1.68, respectively). The proposed major structure for the Fe(ATP)2- complex is the 'open' structure. In the minor 'closed' structure N7 nitrogen is probably coordinated with Fe(II) through a bridging water molecule. The electronic and stereochemical requirements for Fe(II)-coordination with ATP4- were probed using a series of modified-phosphate or modified-adenine ATP analogues. We concluded that: Fe(II) coordinates solely with the phosphate-oxygen atom, and not with sulfur, amine, or borane in the cases of phosphate-modified analogues of ATP; a high electron density on N7 and an anti conformation of the adenine-nucleotide are required for enhanced stability of ATP analogues:Fe(II) complexes as compared to ATP complexes (up to more than 100-fold); there are no stereochemical preferences for Fe(II)-coordination with either Rp or Sp isomers of ATP-alpha-S or ATP-alpha-BH3 analogues.
Richter
Yael
Y
Department of Chemistry, Gonda-Goldschmied Medical Research Center, Bar-Ilan University, Ramat-Gan, Israel.
Fischer
Bilha
B
D000227:Adenine Nucleotides / Q000737:chemistry*; D000244:Adenosine Diphosphate / Q000737:chemistry; D000249:Adenosine Monophosphate / Q000737:chemistry; D000255:Adenosine Triphosphate / Q000737:chemistry; D005296:Ferrous Compounds / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D015341:Nucleic Acid Probes
D000227:Adenine Nucleotides; D005296:Ferrous Compounds; D015341:Nucleic Acid Probes; D000249:Adenosine Monophosphate; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate