title: Structural and functional models of the active site of zinc phosphotriesterase.
abstract: In an attempt to prepare structural and functional models for the active site of the hydrolytic enzyme zinc phosphotriesterase, five new zinc complexes of the ligands 2,6-bis[N-(N-(carboxylmethyl)-N-((1-methylimidazol)methyl)amine)methyl]-4-methylphenolate (BCIMP) and the corresponding asymmetric ligand 2-(N-isopropyl-N-((1-methylimidazolyl)methyl)aminomethyl)-6-(N-carboxylmethyl-N-((1-methylimidazolyl)methyl)aminomethyl)-4-methylphenol (ICIMP) have been synthesized, viz. Na[Zn(2)(BCIMP)Ac(2)] (1), [Zn(2)(BCIMP)(Ph(2)Ac)] (2), [Zn(2)(ICIMP)Ac(2)] (3), [Zn(4)(ICIMP)(2)(Me(3)Ac)(2)][ClO(4)](2) (4), and [Zn(4)(ICIMP)(2)(Ph(2)Ac)(2)][ClO(4)](2) (5). The X-ray structure of complex 5 has been determined and reveals that the complex is a dimer of dimers in the solid state, which in solution dissociates to potent structural models. Studies using NMR show that only one carboxylate coligand bridges the dizinc units in the case of diphenyl acetate and pivalate, while the steric bulk of acetate is sufficiently small to permit the coordination of two acetates/dizinc unit. Functional studies involving the hydrolysis/transesterification of 2-hydroxypropyl p-nitrophenyl phosphate (HPNP) show that the complex with ICIMP (compound 5) has a significantly higher rate of catalysis than the BCIMP complex (compound 2). This is attributed to the vacant/labile coordination site that is available in the ICIMP complex but not the BCIMP complex.
authors.affiliation: Inorganic Chemistry, Kemicentrum, Lund University, Box 124, SE-221 00 Lund, Sweden.
authors.forename: Håkan
authors.initials: H
authors.lastname: Carlsson
authors.forename: Matti
authors.initials: M
authors.lastname: Haukka
authors.forename: Ebbe
authors.initials: E
authors.lastname: Nordlander
mesh_terms: D001665:Binding Sites; D002384:Catalysis; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D007700:Kinetics; D008024:Ligands; D008956:Models, Chemical; D008958:Models, Molecular; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D044345:Phosphoric Triester Hydrolases / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship; D015032:Zinc / Q000737:chemistry*
chemical_list: D008024:Ligands; D009942:Organometallic Compounds; D004247:DNA; D044345:Phosphoric Triester Hydrolases; D015032:Zinc