Modeling the active site structures of vanadate-dependent peroxidases and vanadate-inhibited phosphatases

Abstract

The active center of vanadate-dependent peroxidases (VPOs) is represented by vanadate covalently attached to a histidine, with vanadium in a trigonal-bipyramidal environment. Protein phosphatases and kinases are inhibited by the phosphate analog vanadate [VVO2(OH)2- and VIVO(OH)3-], which can be related to the coordination of vanadium to histidine or a hydroxide function as provided by tyrosinate or serinate. The vanadium centers in these proteins have been modeled by employing chiral ONO ligands. The penta-coordinated chiral complexes [VO(OMe)(L1)] (H2L1 = substituted diethanolamine) are distorted trigonal-bipyramidal with the methoxy group and the amine-N in the axial positions. These structural models of VPO also mimic the sulfide-oxidation activity of the peroxidases. The complexes [VO(H2O)L3] (H2L3 = Schiff-base ligands based on salicylaldehyde derivatives (o-vanillin; 2-hydroxy-naphthylaldehyde) and L- or D,L-tyrosine, or D,L-serine are tetragonal-pyramidal; the OH functions of the amino acid moieties are not directly coordinated to vanadium; they are involved, however, in complex hydrogen-bonding networks. The oxo/peroxo anion [VO(O2)(L2)2]3- (H2L2 = 2,5-dipicolinic acid) contains a slightly asymmetrically bonded O22-, featuring structural characteristics of the peroxo/hydroperoxo intermediates of the peroxidases. XD structure results are reported for the following complexes: R,S- and R,R-[VO(OMe)(L1)], K3[VO(O2)(L2)2].4.5H2O, the Tyr derivatives L-[VO(H2O)L3].MeOH and D,L-[VO(H2O)L3].H2O, and the Ser derivative D,L-[VO(H2O)L3].2H2O.

Unexpected Synthesis of an Unsymmetrical μ-Oxido Divanadium(V) Compound through a Reductive Cleavage of a N−O Bond and Cleavage-Hydrolysis of a C−N Bond of an N,N-Disubstituted Bis-(hydroxylamino) Ligand

“…Vanadium is a bioessential element that is found in two enzyme families, the vanadate-dependent haloperoxidases , and vanadium−nitrogenases . In addition, vanadium is present in remarkably high concentrations in sea squirts , (and fan worms) , and in certain mushrooms of the genus Amanita .…”

Interaction of Vanadyl (VO2+) with Ligands Containing Serine, Tyrosine, and Threonine

“…Because amino acids and oligopeptides do not efficiently coordinate to vanadyl in the absence of auxiliary ligands (such as o -phenanthroline), we have employed the amino acids as Schiff base derivatives, using o -hydroxynaphthadehyde (nap) or o -vanillin (van) as the carbonyl component and thus providing strong ligating properties. Preliminary results on some of these complexes have been published previously . Structurally characterized Schiff base complexes containing amino acids without a function in the side chain include [VO(sal-Ala)H 2 O], [VO(sal-Gly)py 2 ] (sal = salicylidene, py = pyridine),28a and the dinuclear oxovanadium(V) complex [V 2 O 3 (sal-val) 2 H 2 O] 28b…”

Vanadium Thiolate Complexes for Efficient and Selective Sulfoxidation Catalysis: A Mechanistic Investigation

“…Scheme is adapted from the generally accepted catalytic cycle proposed for sulfoxidation by vanadium(IV) or (V) complexes. , The commonly proposed active species is a cis -oxido peroxido vanadium(V) intermediate. Consequently, when considering V IV complexes, the activating step corresponds to their oxidation into V V species, which will correspond to the “real” catalysts.…”