Cation-π versus OH-π Interactions in Proteins:  A Density Functional Study

Abstract

Structure and bonding of a cation-π complex and an OH-π adduct are investigated using density functional theory with gradient-corrections for the exchange-correlation functional. Our calculations are carried out for two specific model complexes representing (i) the thymine/Arg 72 adduct in the ternary complex of HIV-1 reverse transcriptase (RT) with a DNA template primer and a deoxynucleoside triphosphate (Huang, H., et al. Science 1998, 282, 1669-1675 and (ii) the Tyr6-Thr13 adduct in µ-gluthatione transferase (µ-GST) (Xiao, G., et al. Biochemistry 1996, 35, 4753-4765). We find that electrostatic interactions play an important role and provide similar stabilization energies to the two π complexes. In HIV-1 RT, the π electronic density of thymine is essentially uneffected by the presence of the arginine guanidium group; on the contrary, tyrosine is significantly polarized by the interaction with the hydroxyl group and other groups present in the µ-GST enzyme. The influence of Thr13 induced-polarization on Tyr6 pK a is compared with that of other interacting groups at the active site.

TETRAETHYLAMMONIUM BINDING TO THE OUTER MOUTH OF THE KcsA POTASSIUM CHANNEL: IMPLICATIONS FOR ION PERMEATION

“…The interactions between TEA þ methyl groups and Tyr82 side chain is always almost on the same plane of the aromatic ring (Table 3). Therefore, our data provide no evidence of TEA þ =Tyr82 cation-p interactions, [48,49] as previously postulated. [4] To further validate our procedure against experimental data we have constructed a model and carried out MD simulations for the Y82C mutant, whose affinity for TEA þ is know to be lower than that for WT.…”

Structurally Conserved Amino Acid W501 Is Required for RNA Helicase Activity but Is Not Essential for DNA Helicase Activity of Hepatitis C Virus NS3 Protein

“…The OH hydrogen is approximately 2.5 Å from the centroid of the six-member ring and is in a favorable orientation to interact with the face of the ring. Putative -facial interactions have been identified in a number of protein (30) and small-molecule structures (19) and might make important contributions to specificity and enzyme catalysis (10,33). High-level ab initio calculations estimate the interaction energy of these bonds to be approximately 1 to 3 kcal/mol (19,40).…”

Interactions with Aromatic Rings in Chemical and Biological Recognition

“…A rare example of OH/π hydrogen bonding in proteins is provided by the complex of the enzyme glutathione transferase with glutathione (GSH), in which the side chain of Thr 13 is arranged face‐on to the aromatic face of Tyr 6 (Figure 17 b). 185 This interaction decreases the p K a value of the Tyr HO group and strengthens its hydrogen‐bonding capacity to the HS group of GSH, thereby influencing the reactivity of the latter 186. The occurrence of OH/π and NH/π interactions in proteins has been investigated in detail through several PDB searches 187–191.…”