HSpA – Kinetic Mechanisms of Enzyme Inhibition and Activation

Hyperbolic specific activation

**Fingerprints of HSpA: Dependence of the parameters on [X]**

**Fingerprints of HSpA: Specific velocity plot and replot**

Featured examples

K_m↓ The apparent Michaelis constant decreases with increasing [X]

This symbol is shown only when the featured dependence of the parameter on modifier concentration has been demonstrated by the authors.

#	Enzyme Species	EC no.	Modifier	Substrate⁽¹⁾	Name given by authors ⁽²⁾	Reference⁽³⁾
1	Sucrose α-glucosidase ⁽⁴⁾ Mus musculus (Balb c)	3.2.1.48	Na⁺ (pH = 7.2)	Sucrose	Pure K-type system, K_m↓ α = 0.76, β = 1, K_X = 8.79 mM	Gupta (2009)
2	Sucrose α-glucosidase Rattus norvegicus	3.2.1.48	Na⁺ (pH = 5.4)	Sucrose	K-type activation, K_m↓ ⁽⁵⁾ α = 0.02, β = 1, K_X = 39 mM	Semenza (1969)
3	Sucrose α-glucosidase Hamster (species not specified)	3.2.1.48	Na⁺ (pH = 5.4)	Sucrose	K-type activation, K_m↓ ⁽⁵⁾ α = 0.06, β = 1, K_X = 13 mM	Semenza (1969)
4	5'-Nucleotidase Legionella pneumophila	3.1.3.5	GTP	GMP	K-type activation, K_m↓ α = 0.7, β = 1	Srinivasan (2014)
5	1-Phosphatidylinositol phosphodiesterase Bacillus cereus	3.1.4.10	Dihexanoylphosphatidylcholine and Butyl-fluorescein myo-inositol phosphate	Butyl-fluorescein myo-inositol phosphate ⁽⁶⁾	Activation α' = 0.2, β' = 1.4, K_s = 0.5 mM, K'_s = 0.15 mM α = 0.03, β = 1.0, K_A = 0.2 mM	Birrell (2003)

⁽¹⁾ Always the varied substrate. In two- or more-substrate reactions the concentration(s) of the non varied substrate(s) is/are kept constant.

⁽²⁾ Name of the mechanism given by the authors in the quoted reference. α, β and the inhibition/activation constants for the modifier (X), uniformly denoted K_X, are the values specified by the authors. In some cases, missing parameters have been calculated from graphical or tabular data provided in the papers. In two- or more-substrate reactions, K_X represents an apparent constant at given concentrations of the fixed substrates and no calculations of the intrinsic values have been attempted.

⁽³⁾ Full references at the end of the page provide also the digital object identifier (doi), if available. Clicking the authors (highlighted) opens the reference in PubMed.

⁽⁴⁾ The mechanism is species- and pH-dependent, See also under HMx(Sp=Ca)I and HMx(Sp=Ca)A.

⁽⁵⁾ Parameters calculated from the data in Fig. 3 (Semenza, 1969).

⁽⁶⁾ Symbols as in the original paper [Birrell (2003), free full text, see References]. The enzyme is a small monomeric molecule with a catalytic site and an allosteric site that can bind either a second molecule of substrate, which triggers nonessential activation with mechanism hyperbolic mixed, predominantly catalytic activation [see entry 11 in HMx(Sp<Ca)A], or the activator dihexanoylphosphatidylcholine with mechanism HSpA. The parameters in this page refer to a reaction in the presence of both reactants. Clicking the reference Birrell (2003) below allows to visualize the entire mechanism, made up by reactions schemes A and B acting together.

References

Birrell GB, Zaikova TO, Rukavishnikov AV, Keana JFW, Hayes Griffith O (2003) Allosteric interactions within subsites of a monomeric enzyme: Kinetics of fluorogenic substrates of PI-specific phospholipase C. Biophys J 84: 3264-3275. doi:10.1016/S0006-3495(03)70051-4
Gupta S, Mahmood S, Mahmood A (2009) Kinetic characteristics of brush border sucrase activation by Na+ ions in mice intestine. Indian J Exp Biol 47: 811-815.
Semenza G (1969) A kinetic investigation on the allosteric effects in intestinal sucrase. Eur J Biochem 8: 518-529. doi:10.1111/j.1432-1033.1969.tb00557.x,
Srinivasan B, Forouhar F, Shukla A, Sampangi C, Kulkarni S, Abashidze M, Seetharaman J, Lew S, Mao L, Acton TB, Xiao R, Everett JK, Montelione GT, Tong L, Balaram H (2014) Allosteric regulation and substrate activation in cytosolic nucleotidase II from Legionella pneumophila. FEBS J 281: 1613-1628. doi:10.1111/febs.12727