Fluoride inhibition of enolase: crystal structure and thermodynamics.

  title={Fluoride inhibition of enolase: crystal structure and thermodynamics.},
  author={Jie Qin and Geqing Chai and John M. Brewer and Leslie L. Lovelace and Lukasz Lebioda},
  volume={45 3},
Enolase is a dimeric metal-activated metalloenzyme which uses two magnesium ions per subunit: the strongly bound conformational ion and the catalytic ion that binds to the enzyme-substrate complex inducing catalysis. The crystal structure of the human neuronal enolase-Mg2F2P(i) complex (enolase fluoride/phosphate inhibitory complex, EFPIC) determined at 1.36 A resolution shows that the combination of anions effectively mimics an intermediate state in catalysis. The phosphate ion binds in the… Expand
Effect of ions and inhibitors on the catalytic activity and structural stability of S. aureus enolase
The glycolytic enzyme enolase of Staphylococcus aureus is a highly conserved enzyme which binds to human plasminogen thereby aiding the infection process and the circular dichroism data indicate that other than Hg2+ and to a certain extent Cu2+, none of the other ions destabilized rSaeno. Expand
Crystal Structures of Pyrophosphatase from Acinetobacter baumannii: Snapshots of Pyrophosphate Binding and Identification of a Phosphorylated Enzyme Intermediate
  • Y. Si, X. Wang, +6 authors J. Su
  • Chemistry, Medicine
  • International journal of molecular sciences
  • 2019
The mass spectroscopy results have identified a highly conserved lysine residue (Lys30) in the catalytic center that is phosphorylated, indicating that the enzyme could form a phosphoryl enzyme intermediate during hydrolysis. Expand
Substrate-to-Product Conversion Facilitates Active Site Loop Opening in Yeast Enolase: A Molecular Dynamics Study.
Microsecond molecular dynamics simulations of the protein-substrate and protein-product complexes are conducted to elucidate the mechanism of the opening of catalytically important active site loops, indicating that conversion of substrate to product is accompanied by diminished metal coordination and hydrogen-bonding interactions, as well as enhanced loop flexibility. Expand
Catalytic properties of the metal ion variants of mandelate racemase reveal alterations in the apparent electrophilicity of the metal cofactor.
Viscosity variation experiments with Mn2+-MR showed that the metal ion plays a role in the uniform binding of the transition states for enzyme-substrate association, the chemical step, and enzyme-product dissociation, resulting in a levelling effect relative to the trends observed for the free metals in solution. Expand
Structures of asymmetric complexes of human neuron specific enolase with resolved substrate and product and an analogous complex with two inhibitors indicate subunit interaction and inhibitor cooperativity.
Kinetic studies showed that the inhibition of NSE by mixture of TSP and LAP is stronger than predicted for independently acting inhibitors, indicating that in some cases inhibition of homodimeric enzymes by mixtures of inhibitors ("heteroinhibition") may offer advantages over single inhibitors. Expand
Thermal unfolding of apo- and holo-enolase from Saccharomyces cerevisiae: different mechanisms, similar activation enthalpies.
The results indicate smaller unfolding rate-constants in the presence of Mg(2+), thus favoring the native state of yeast enolase, and the temperature dependence of the unfolding rates allowed us to calculate the activation enthalpies of denaturation. Expand
Census of halide-binding sites in protein structures
A pipeline for the quick analysis of halide-binding sites in proteins using the available software and revealed that all of halides are strongly attracted by the guanidinium moiety of arginine side chains, however, there are also certain preferences among halides for other partners. Expand
Fluoride inhibition of Sporosarcina pasteurii urease: structure and thermodynamics
Urease is a nickel-dependent enzyme and a virulence factor for ureolytic bacterial human pathogens, but it is also necessary to convert urea, the most worldwide used fertilizer, into forms ofExpand
Structural flexibility in Trypanosoma brucei enolase revealed by X‐ray crystallography and molecular dynamics
Six new crystal structures of enolase are determined, in various ligation states and conformations, and a striking structural diversity of loops near the catalytic site is shown, for which variation can be interpreted as distinct modes of conformational variability that are explored during the molecular dynamics simulations. Expand
Fluoride-dependent interruption of the transport cycle of a CLC Cl−/H+ antiporter
Examination of various mutant antiporters implies a “lock-down” mechanism of F− inhibition, in which F−, by virtue of its unique H-bonding chemistry, greatly retards a proton-linked conformational change essential for the transport cycle of CLC-ec1. Expand