Figure 1.
Electrostatic and spatial pertubations in different enzymes on ligand binding.
Perturbations for each residue is computed with respect to residues within a radial distance of 6A. (a) and (b) Diphtheria toxin repressor (holoenzyme:1BI3/apoenzyme:1BI2), (c) and (d) Hemoglobin WT (holoen-zyme:3SDH/apoenzyme:4SDH) Hemoglobin K96R (holoenzyme:3UHI/apoenzyme:3UHK), (e) and (f) Fructose 1,6-bisphosphatase (holoenzyme:1EYK/apoenzyme:1CNQ), (g) and (h) Ketosteroid isomerase (holoenzyme:3IPT/apoenzyme:1OPY), (i) and (j) Cu-Zn superoxide dismutase WT (holoenzyme:1HL5/apoenzyme:1HL4), and mutant A4V (holoenzyme:1UXM/apoenzyme:1HL5)
Table 1.
Residue pairs that undergo significant polarity reversal: PD1 and PD2 are the electrostatic potential difference between residues `a' and `b' in the holoenzyme and apoenzyme, respectively.
Figure 2.
Visualizing the residues/domains that undergo significant electrostatic perturbation in the diphtheria toxin repressor (PDBid:1BI3).
Threshold value above which perturbation are considered significant is 200 potential (difference) units. It can be seen that the C-terminal undergoes more electrostatic changes than the N-terminal. (a) Residues undergoing electrostatic perturbation of magnitude greater than the threshold value are colored in red and yellow (Met10). Met10 ligands metal ions, and its mutation to alanine results in complete inactivation of repressor activity. (b) Residues undergoing positive and negative electrostatic perturbations greater than the threshold value are colored in red and blue respectively. As expected, they are interspersed in order to maintain electrostatic homogeneity.
Figure 3.
Residues involved in intersubunit coupling in hemoglobin (PDBid:3SDH).
Lys96 (in green) in one subunit is in close proximity to His69 (in red) in the neighboring subunit. MEPP detects significant electrostatic perturbation in His69 and not in Lys96. On the other hand, Lys96 undergoes a distinct conformational change.
Figure 4.
Residues involved in intersubunit interactions in Cu-Zn superoxide dismutase (PDBid:1HL5).
(a) Glu77 (in red) and Arg69 (in blue) undergo significant perturbation. It can be seen that Glu77, which gains positive potential with respect to residues in the vicinity, is physically close to Glu77 from other subunits, and possibly generates a repulsive force that destabilizes the structure. (b) Asn86 (in green) and Lys128 (in yellow) from neighboring subunits are seen to be closely placed to each other, and are involved in H-bonds. Conformational changes in Lys128 possibly disrupt these bonds.