Role of hydrophobicity in the binding of coenzymes. Appendix. Translational and rotational contribution to the free energy of dissociation.
We calculate the loss of surface area accessible to solvent associated with coenzyme binding in Clostridium flavodoxin, in dogfish lactate dehydrogenase, and in lobster glyceraldehyde-3-phosphate dehydrogenase. The coenzymes are nearly buried in the complexes and lose on the order of 600 A2, while the proteins lose a similar amount of accessible surface area. Some of the loss can be attributed to conformation changes in the protein, at least in the case of lactate dehydrogenase, where we show that the apoenzyme has a larger accessible surface area than the holoenzyme. Using known correlations with the hydrophobic contribution to the free energy, we demonstrate that hydrophobicity is the major source of stabilization free energy in FMN binding to flavodoxin and in NAD binding to the two dehydrogenases: it contributes 25 to 30 kcal/mol to the free energy of dissociation, more than required in order to compensate for the loss of six degrees of translational/rotational freedom by the coenzyme.
D000818:Animals; D003013:Clostridium; D004284:Dogfish; D005486:Flavin Mononucleotide; D005418:Flavodoxin; D005420:Flavoproteins; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D007770:L-Lactate Dehydrogenase; D008433:Mathematics; D009243:NAD; D008121:Nephropidae; D011485:Protein Binding; D013816:Thermodynamics
D005418:Flavodoxin; D005420:Flavoproteins; D009243:NAD; D005486:Flavin Mononucleotide; D007770:L-Lactate Dehydrogenase; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases