Organic Vanadium Compounds - Transition State Analogy with Organic Phosphorus Compounds

Crans, Debbie C.; Keramidas, Anastasios D.; Drouza, Chryssoula

doi:10.1080/10426509608046244

Cited by 11 publications

(40 citation statements)

References 1 publication

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In fact, vanadate has been used as a transition state analog in several enzyme-catalyzed reactions including phosphomonoester hydrolysis by rat acid phosphatase and ribonucleotide phosphodiester hydrolysis by ribonuclease A (2, 3). Vanadate is isostructural and isoelectronic with phosphate, a product, and a competitive inhibitor of alkaline phosphatase (4). Unlike the phosphate ion, vanadate can form stable five-coordinate species (4) allowing it to serve as a transition state analog for both the acquisition of phosphate and its release in the catalytic reaction of alkaline phosphatase.…”

Section: Escherichia Coli Alkaline Phosphatase (Ap)mentioning

confidence: 99%

A Model of the Transition State in the Alkaline Phosphatase Reaction

Holtz

Stec

Kantrowitz³

1999

Journal of Biological Chemistry

175

207

View full text Add to dashboard Cite

A high resolution crystal structure of Escherichia coli alkaline phosphatase in the presence of vanadate has been refined to 1.9 Å resolution. The vanadate ion takes on a trigonal bipyramidal geometry and is covalently bound by the active site serine nucleophile. A coordinated water molecule occupies the axial position opposite the serine nucleophile, whereas the equatorial oxygen atoms of the vanadate ion are stabilized by interactions with both Arg-166 and the zinc metal ions of the active site. This structural complex supports the in-line displacement mechanism of phosphomonoester hydrolysis by alkaline phosphatase and provides a model for the proposed transition state in the enzymecatalyzed reaction. Escherichia coli alkaline phosphatase (AP)1 is a homodimeric metalloenzyme catalyzing the nonspecific hydrolysis of phosphate monoesters into inorganic phosphate and an alcohol. The overall structure is approximately 100 Å ϫ 50 Å ϫ 50 Å with the active sites 30 Å apart from each other on opposite sides of the molecule. Each active site contains two tightly bound zinc ions (Zn 1 and Zn 2 ) and one magnesium ion. The three closely spaced metal binding sites trace a triangle with the two zinc ions 4 Å apart and the magnesium binding site approximately 5 Å from Zn 2 and 7 Å from Zn 1 . The active site pocket shown in Fig. 1 (top panel) with bound inorganic phosphate is shallow and, in addition to the three metal ions, is lined by Arg-166 and Ser-102.Based on the structure of the enzyme with phosphate bound, Kim and Wyckoff (1) have proposed the reaction mechanism shown in Scheme 1. The free enzyme interacts with a phosphomonoester (ROP) to form the Michaelis enzyme-substrate complex (E⅐ROP). This complex breaks down upon nucleophilic attack of Ser-102 on the phosphate group of the substrate forming the covalent phospho-enzyme intermediate (E-P). This covalent intermediate is subsequently hydrolyzed into the noncovalent enzyme-phosphate complex (E⅐P i ). As predicted by the mechanism, the reaction proceeds with overall retention of configuration at the phosphorus center. The two consecutive in-line displacement steps are postulated to have trigonal bipyramidal transition states.In this study the interaction between vanadate (i.e. orthovanadate, VO 4 3Ϫ ) and E. coli alkaline phosphatase (EC 3.1.3.1) is evaluated by x-ray crystallography. Vanadate, an oxyanion of pentavalent vanadium, readily adopts a five-coordinate geometry resembling the proposed transition state in the enzyme-catalyzed reaction of alkaline phosphatase. In fact, vanadate has been used as a transition state analog in several enzyme-catalyzed reactions including phosphomonoester hydrolysis by rat acid phosphatase and ribonucleotide phosphodiester hydrolysis by ribonuclease A (2, 3). Vanadate is isostructural and isoelectronic with phosphate, a product, and a competitive inhibitor of alkaline phosphatase (4). Unlike the phosphate ion, vanadate can form stable five-coordinate species (4) allowing it to serve as a transition state analog for both the ac...

show abstract

Section: Escherichia Coli Alkaline Phosphatase (Ap)mentioning

confidence: 99%

A Model of the Transition State in the Alkaline Phosphatase Reaction

Holtz

Stec

Kantrowitz³

1999

Journal of Biological Chemistry

175

207

View full text Add to dashboard Cite

show abstract

“…6 A range of studies of a few vanadium compounds on isolated enzyme systems have been reported where the species exerting the effects can be more rigorously tracked. 5,21,22 Most of these studies were carried out with phosphatases and kinases, 21,22 but some studies with proteins in other metabolic pathways 5,23,24 including the Ca…”

Section: Introductionmentioning

confidence: 99%

Sarcoplasmic Reticulum Calcium ATPase Is Inhibited by Organic Vanadium Coordination Compounds: Pyridine-2,6-dicarboxylatodioxovanadium(V), BMOV, and an Amavadine Analogue

et al. 2008

View full text Add to dashboard Cite

The general affinity of the sarcoplasmic reticulum (SR) Ca 2+ -ATPase was examined for three different classes of vanadium coordination complexes including a vanadium(V) compound, pyridine-2,6-dicarboxylatodioxovanadium(V) (PDC-V(V)), and two vanadium(IV) compounds, bis(maltolato)oxovanadium(IV) (BMOV), and an analogue of amavadine, bis(N-hydroxylamidoiminodiacetato)vanadium(IV) (HAIDA-V(IV)). The ability of vanadate to act either as a phosphate analogue or as a transition-state analogue with enzymes' catalysis phosphoryl group transfer suggests that vanadium coordination compounds may reveal mechanistic preferences in these classes of enzymes. Two of these compounds investigated, PDC-V(V) and BMOV, were hydrolytically and oxidatively reactive at neutral pH, and one, HAIDA-V(IV), does not hydrolyze, oxidize, or otherwise decompose to a measurable extent during the enzyme assay. The SR Ca 2+ -ATPase was inhibited by all three of these complexes. The relative order of inhibition was PDC-V(V) > BMOV > vanadate > HAIDA-V(IV), and the IC 50 values were 25, 40, 80, and 325 µM, respectively. Because the observed inhibition is more potent for PDC-V(V) and BMOV than that of oxovanadates, the inhibition cannot be explained by oxovanadate formation during enzyme assays. Furthermore, the hydrolytically and redox stable amavadine analogue HAIDA-V(IV) inhibited the Ca 2+ -ATPase less than oxovanadates. To gauge the importance of the lipid environment, studies of oxidized BMOV in microemulsions were performed and showed that this system remained in the aqueous pool even though PDC-V(V) is able to penetrate lipid interfaces. These findings suggest that the hydrolytic properties of these complexes may be important in the inhibition of the calcium pump. Our results show that two simple coordination complexes with known insulin enhancing effects can invoke a response in calcium homeostasis and the regulation of muscle contraction through the SR Ca 2+ -ATPase.

show abstract

“…In some instances, vanadium complexes act as better in vivo inhibitors than inorganic sources of vanadium because the greater lipophilicity of the complex allows for better cell membrane permeability [13]. Significantly stronger inhibition by some of the vanadyl-b-diketone complexes was not observed in the in vitro studies reported here, e.g.…”

Section: Resultsmentioning

confidence: 39%

“…An X-ray crystal structure for E. coli APase with vanadate bound in both active sites reveals that vanadium's coordination geometry is trigonal bipyramidal with a serine nucleophile and coordinated water occupying the axial positions [12]. Crans and co-workers have pointed out the importance of considering vanadium's solution chemistry when using vanadium compounds as tools in biological studies [13]. An investigation of chicken-intestine APase inhibition by vanadium-dipicolinate complexes, for example, revealed that assay conditions must be controlled to obtain meaningful data [13].…”

Section: Introductionmentioning

confidence: 99%

“…Crans and co-workers have pointed out the importance of considering vanadium's solution chemistry when using vanadium compounds as tools in biological studies [13]. An investigation of chicken-intestine APase inhibition by vanadium-dipicolinate complexes, for example, revealed that assay conditions must be controlled to obtain meaningful data [13].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Alkaline phosphatase inhibition by vanadyl-β-diketone complexes: electron density effects

Ziegler

Florián

Ballícora

et al. 2008

Journal of Enzyme Inhibition and Medicinal Chemistry

View full text Add to dashboard Cite

A series of systematically modified vanadyl-b-diketone complexes, VO(b-diketone) 2 , bearing substituent groups with different electron inductive properties were synthesized and evaluated as inhibitors against calf-intestine alkaline phosphatase (APase). A combination of biochemical and quantum mechanical techniques were employed to identify structure-activity relationships relevant for rational design of phosphatase inhibitors. Kinetic parameters and activation free energy, enthalpy, and entropy for calf-intestine APase-catalyzed dephosphorylation of para-nitrophenylphosphate were also determined along with the inhibition constants (K i ) for the VO(b-diketone) 2 complexes. Increased positive charge on the vanadyl group increases the inhibition potency of the complex while the absence of an available coordination site on the complex decreases its inhibition potency. These findings correlate well with the results of ab initio electron density calculations for the complexes.

show abstract

Organic Vanadium Compounds - Transition State Analogy with Organic Phosphorus Compounds

Cited by 11 publications

References 1 publication

A Model of the Transition State in the Alkaline Phosphatase Reaction

A Model of the Transition State in the Alkaline Phosphatase Reaction

Sarcoplasmic Reticulum Calcium ATPase Is Inhibited by Organic Vanadium Coordination Compounds: Pyridine-2,6-dicarboxylatodioxovanadium(V), BMOV, and an Amavadine Analogue

Alkaline phosphatase inhibition by vanadyl-β-diketone complexes: electron density effects

Contact Info

Product

Resources

About