Multiple Intermolecular Interaction Modes of Positively Charged Residues with Adenine in ATP-Binding Proteins

Abstract

Adenosine 5'-triphosphate (ATP) plays an essential role in all forms of life. Molecular recognition of ATP in ATP-binding proteins is a subject of great importance for understanding enzymatic mechanisms and for drug design. We have carried out a large-scale data mining of the Protein Data Bank (PDB) to analyze molecular determinants for recognition of ATP, in particular, the adenine base, by ATP-binding proteins. A novel distribution pattern of charged residues around the adenine base was discovered: lysine residues tend to occupy the major groove N7 side of the adenine base, and the arginine residues situate preferentially above or below the adenine bases. Such an arrangement is advantageous because it facilitates multiple modes of intermolecular interactions, that is, cation-pi interactions and a hydrogen bond between lysine and adenine, and cation-pi and pi-pi stacking interactions between arginine and adenine. For the two representative Lys... Adenine and Arg... Adenine interactions, intermolecular interaction energies were subsequently analyzed by means of the supermolecular approach at the MP2 level with solvation free energy correction using the SM5.42R model of Cramer and Truhlar, which gave rise to significant interaction strengths.

Structures of lipoyl synthase reveal a compact active site for controlling sequential sulfur insertion reactions

“…Finally, the guanidino group of Arg281 is positioned to make a π-cation interaction with the other face of the aromatic adenine base ( Figure 3C). This is a well characterized mode of interaction for the recognition of adenosyl ligands [45], but has not previously been observed for the RS enzyme superfamily.…”

Divergent DNA-Binding Specificities of a Group of ETHYLENE RESPONSE FACTOR Transcription Factors Involved in Plant Defense

“…9B). Such pairings between Lys and adenine are prevalent in reported structures (Mao et al, 2003). ERF189 also recognizes P-type sequences without the TA pair (Table I), and its specificity for the P box did not show a firm preference for a TA pair at the position (Fig.…”

The Molecular Basis for Cyclopiazonic Acid Inhibition of the Sarcoplasmic Reticulum Calcium Pump

“…Interestingly, this latter residue in the Na -ATPase (SPCA1) is substituted with a serine, another amino acid commonly found in adenine recognition motifs (48). Approximately one-third of ATP-dependent proteins contain an adenine recognition motif (48,50) that is similar to the binding site in our E2(CPA) model. The two arginines found in Ca 2ϩ -ATPase closely resemble the adenine recognition motif in a 70-kDa heat shock protein (Protein Data Bank code 1BUP) (51).…”

“…678 may participate in a cation-interaction. The cation-interaction of positively charged residues is a common mechanism for the molecular recognition of adenine (48,49). Arg 678 appears to fit this role, because it is highly conserved among members of the P-type ATPases, whereas Arg 489 is not (Fig.…”