The catalytic role of INCENP in Aurora B activation and the kinetic mechanism of Aurora B/INCENP

2008 ◽  
Vol 417 (1) ◽  
pp. 355-360 ◽  
Author(s):  
Jingsong Yang ◽  
Francesca Zappacosta ◽  
Roland S. Annan ◽  
Kelvin Nurse ◽  
Peter J. Tummino ◽  
...  
Keyword(s):  
Cellular Localization ◽  
Specific Activity ◽  
Kinetic Mechanism ◽  
Aurora B ◽  
Peptide Substrate ◽  
Catalytic Role ◽  
Substrate Phosphorylation ◽  
Kinetics Of ◽  
Loop Residue

Aurora kinases are a family of serine/threonine protein kinases that play essential roles in mitosis and cytokinesis. AurB (Aurora B kinase) has shown a clear link to cancer and is being pursued as an attractive cancer target. Multiple small molecules targeting AurB have entered the clinic for the treatment of cancer. A protein cofactor, INCENP (inner centromere protein), regulates the cellular localization and activation of AurB. In the present study, we examined the effect of INCENP on the activation kinetics of AurB and also elucidated the kinetic mechanism of AurB-catalysed substrate phosphorylation. We have concluded that: (i) substoichoimetric concentrations of INCENP are sufficient for AurB autophosphorylation at the activation loop residue Thr232, and hence INCENP plays a catalytic role in AurB autophosphorylation; (ii) AurB/INCENP-catalysed phosphorylation of a peptide substrate proceeds through a rapid equilibrium random Bi Bi kinetic mechanism; and (iii) INCENP has relatively minor effects on the specific activity of AurB using a peptide substrate when compared with its role in AurB autoactivation. These results indicate that the effects of INCENP, and probably accessory proteins in general, may differ when enzymes are acting on different downstream targets.

Detailed kinetics of hydrogen abstraction from trans-decalin by OH radicals: the role of hindered internal rotation treatment

2020 ◽  
Vol 22 (44) ◽  
pp. 25740-25746
Author(s):  
Tam V.-T. Mai ◽  
Lam K. Huynh
Keyword(s):  
Master Equation ◽  
Hydrogen Abstraction ◽  
Kinetic Mechanism ◽  
Oh Radicals ◽  
Rate Model ◽  
Wide Range ◽  
Detailed Kinetics ◽  
Kinetics Of ◽  
Detailed Kinetic Mechanism

The detailed kinetic mechanism of the trans-decalin + OH reaction is firstly investigated for a wide range of conditions (T = 200–2000 K & P = 0.76–76000 Torr) using the M06-2X/aug-cc-pVTZ level and stochastic RRKM-based Master equation rate model.

scholarly journals Purification and kinetic mechanism of the major glutathione S-transferase from bovine brain

1989 ◽  
Vol 257 (2) ◽  
pp. 541-548 ◽  
Author(s):  
P R Young ◽  
A V Briedis
Keyword(s):  
Decanoic Acid ◽  
Kinetic Mechanism ◽  
Order Rate Constant ◽  
Bovine Brain ◽  
Glutathione S Transferase ◽  
Rate Acceleration ◽  
Hydrophobic Binding ◽  
Kinetics Of ◽  
Kinetics Of Inhibition

The major glutathione S-transferase isoenzyme from bovine brain was isolated and purified approx. 500-fold. The enzyme has a pI of 7.39 +/- 0.02 and consists of two non-identical subunits having apparent Mr values of 22,000 and 24,000. The enzyme is uniformly distributed in brain, and kinetic data at pH 6.5 with 1-chloro-2,4-dinitrobenzene (CDNB) as substrate suggest a random rapid-equilibrium mechanism. The kinetics of inhibition by product, by GSH analogues and by NADH are consistent with the suggested mechanism and require inhibitor binding to several different enzyme forms. Long-chain fatty acids are excellent inhibitors of the enzyme, and values of 1nKi for hexanoic acid, octanoic acid, decanoic acid and lauric acid form a linear series when plotted as a function of alkyl chain length. A free-energy change of -1900 J/mol (-455 cal/mol) per CH2 unit is calculated for the contribution of hydrophobic binding energy to the inhibition constants. The turnover number of the purified enzyme dimer is approx. 3400/min. When compared with the second-order rate constant for the reaction between CDNB and GSH, the enzyme is providing a rate acceleration of about 1000-fold. The role of entropic contributions to this small rate acceleration is discussed.

Superior catalytic effect of TiF3 over TiCl3 in improving the hydrogen sorption kinetics of MgH2: Catalytic role of fluorine anion

2009 ◽  
Vol 57 (7) ◽  
pp. 2250-2258 ◽  
Author(s):  
L.-P. Ma ◽  
X.-D. Kang ◽  
H.-B. Dai ◽  
Y. Liang ◽  
Z.-Z. Fang ◽  
...  
Keyword(s):  
Catalytic Effect ◽  
Sorption Kinetics ◽  
Hydrogen Sorption ◽  
Catalytic Role ◽  
Kinetics Of ◽  
Fluorine Anion

scholarly journals Flexible pivoting of dynamin PH-domain catalyzes fission: Insights into molecular degrees of freedom

2021 ◽  
pp. mbc.E20-12-0794
Author(s):  
Krishnakanth Baratam ◽  
Kirtika Jha ◽  
Anand Srivastava
Keyword(s):  
Degrees Of Freedom ◽  
Pleckstrin Homology Domain ◽  
Ph Domain ◽  
Vesicle Recycling ◽  
Membrane Fission ◽  
Variable Loops ◽  
Catalytic Role ◽  
Rapid Kinetics ◽  
Kinetics Of

The neuronal dynamin1 functions in the release of synaptic vesicles by orchestrating the process of GTPase dependent membrane fission. Dynamin1 associates with the plasma membrane-localized phosphatidylinositol-4,5-bisphosphate (PIP2) through the centrally-located pleckstrin homology domain (PHD). The PHD is dispensable as fission (in model membranes) can be managed, even when the PHD-PIP2 interaction is replaced by a generic polyhistidine- or polylysine-lipid interaction. However, the absence of the PHD renders a dramatic dampening of the rate of fission. These observations suggest that the PHD-PIP2 containing membrane interaction could have evolved to expedite fission to fulfill the requirement of rapid kinetics of synaptic vesicle recycling. Here, we use a suite of multiscale modeling approaches to explore PHD-membrane interactions. Our results reveal that (a) the binding of PHD to PIP2-containing membranes modulates the lipids towards fission-favoring conformations and softens the membrane, and (b) PHD associates with membrane in multiple orientations using variable loops as pivots. We identify a new loop (VL4), which acts as an auxiliary pivot and modulates the orientation flexibility of PHD on the membrane — a mechanism we believe may be important for high fidelity dynamin collar assembly. Together, these insights provide a molecular-level understanding of the catalytic role of PHD in dynamin-mediated membrane fission. [Media: see text] [Media: see text] [Media: see text] [Media: see text]

Thermodynamic and Kinetic Investigation of the Solvent Effect on the Oxidation of [Co(en)2SCH2COO]+ with S2O82- In Water-Methanol and Water-tert-Butyl Alcohol Mixtures

1993 ◽  
Vol 58 (5) ◽  
pp. 1001-1006 ◽  
Author(s):  
Oľga Vollárová ◽  
Ján Benko
Keyword(s):  
Transfer Functions ◽  
Activation Parameters ◽  
Butyl Alcohol ◽  
Oxidation Of Co ◽  
Kinetics Of Oxidation ◽  
Tert Butyl ◽  
Tert Butyl Alcohol ◽  
Alcohol Mixtures ◽  
Kinetics Of

The kinetics of oxidation of [Co(en)2SCH2COO]+ with S2O82- was studied in water-methanol and water-tert-butyl alcohol mixtures. Changes in the reaction activation parameters ∆H≠ and ∆S≠ with varying concentration of the co-solvent depend on the kind of the latter, which points to a significant role of salvation effects. The solvation effect on the reaction is discussed based on a comparison of the transfer functions ∆Ht0, ∆St0 and ∆Gt0 for the initial and transition states with the changes in the activation parameters accompanying changes in the CO-solvent concentration. The transfer enthalpies of the reactant were obtained from calorimetric measurements.

Sign in / Sign up

Export Citation Format

Share Document