Substrate-protein interaction energy in the enzyme phenylalanine hydroxylase: DFT and ab initio results

Academic Article

Abstract

  • The enzyme phenylalanine hydroxylase catalyzes the conversion of phenylalanine to tyrosine, which is in turn converted to a series of neurologically important compounds. These compounds can then inhibit the initial metabolism of phenylalanine by docking in the phenylalanine hydroxylase active site. We use second order Moller-Plesset theory (MP2) and several Density Functional Theory methods to estimate the contribution to the total substrate/protein interaction energy from the electrostatic and dispersion interactions between the substrate and Phe254 in the enzyme. We then study several mutations at the residue 254 site. Our results for one mutation, F254I, agree with an observed loss of function of phenylalanine hydroxylase. We predict several additional mutations that may also cause loss of function in the enzyme. © 2007 Elsevier B.V. All rights reserved.
  • Digital Object Identifier (doi)

    Author List

  • Hofto ME; Godfrey-Kittle A; Cafiero M
  • Start Page

  • 125
  • End Page

  • 130
  • Volume

  • 809
  • Issue

  • 1-3