Electro-nuclear double resonance spectroscopic evidence for a hydroxo-bridge nucleophile involved in catalysis by a dinuclear hydrolase

J Am Chem Soc. 2002 Mar 20;124(11):2595-603. doi: 10.1021/ja003169l.

Abstract

Despite the current availability of several crystal structures of purple acid phosphatases, to date there is no direct evidence for solvent-derived ligands occupying terminal positions in the active enzyme. This is of central importance, because catalysis has been shown to proceed through the direct attack on a metal-bound phosphate ester by a metal-activated solvent-derived moiety, which has been proposed to be either (i) a hydroxide ligand terminally bound to the ferric center or (ii) a bridging hydroxide. In this work we use (2)H Q-band (35 GHz) pulsed electron-nuclear double resonance (ENDOR) spectroscopy to identify solvent molecules coordinated to the active mixed-valence (Fe(3+)Fe(2+)) form of the dimetal center of uteroferrin (Uf), as well as to its complexes with the anions MoO(4), AsO(4), and PO(4). The solvent-derived coordination of the dinuclear center of Uf as deduced from ENDOR data includes a bridging hydroxide and a terminal water/hydroxide bound to Fe(2+) but no terminal water/hydroxide bound to Fe(3+). The terminal water is lost upon anion binding while the hydroxyl bridge remains. These results are not compatible with a hydrolysis mechanism involving a terminal Fe(3+)-bound nucleophile, but they are consistent with a mechanism that relies on the bridging hydroxide as the nucleophile.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acid Phosphatase
  • Arsenates / chemistry
  • Arsenates / metabolism
  • Binding Sites
  • Catalysis
  • Hydrolases / chemistry*
  • Hydrolases / metabolism
  • Iron / chemistry
  • Iron / metabolism
  • Isoenzymes
  • Metalloproteins / chemistry*
  • Metalloproteins / metabolism
  • Molybdenum / chemistry
  • Molybdenum / metabolism
  • Nuclear Magnetic Resonance, Biomolecular / methods
  • Phosphates / chemistry
  • Phosphates / metabolism
  • Solvents
  • Tartrate-Resistant Acid Phosphatase
  • Water / chemistry
  • Water / metabolism

Substances

  • Arsenates
  • Isoenzymes
  • Metalloproteins
  • Phosphates
  • Solvents
  • Water
  • molybdate
  • Molybdenum
  • Iron
  • Hydrolases
  • Acid Phosphatase
  • Tartrate-Resistant Acid Phosphatase
  • arsenic acid