Hyperbolic mixed, balanced activation

Featured examples

V ↑ (∴ k_cat↑)       The apparent limiting rate, and therefore the catalytic constant, increase with increasing [X]

These symbols are shown only when the featured dependencies of the parameters on modifier concentration have 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 = 5.0)	Sucrose	V-type activation, V↑ α = 1, β ≈ 2.6, KX not calculated	Gupta (2009)
2	Trypsin Bos taurus	3.4.21.4	Methylammonium 0.1 M KCl	Acetyl-Gly ethyl ester	Activation, V↑ α = 1, β ≈ 3.2, KX = 380 mM	Inagami (1964)
3	Trypsin Bos taurus	3.4.21.4	Ethylammonium 0.1 M KCl	Acetyl-Gly ethyl ester	Activation, V↑ α = 1, β ≈ 9.5, KX = 69 mM	Inagami (1964)
4	Trypsin Bos taurus	3.4.21.4	1-Propylammonium 0.1 M KCl	Acetyl-Gly ethyl ester	Activation, V↑ α = 1, β ≈ 2.4, KX = 86 mM	Inagami (1964)
5	Trypsin Bos taurus	3.4.21.4	Methylguanidine	Acetyl-Gly ethyl ester	Activation, V↑ α = 1, β ≈ 7, KX = 13 mM	Inagami (1968)
6	Trypsin Bos taurus	3.4.21.4	Ethylguanidine	Acetyl-Gly ethyl ester	Activation, V↑ α = 1, β ≈ 2, KX = 2 mM	Inagami (1968)
7	Myeloblastin Homo sapiens	3.4.21.76	Chondroitin sulfate	MeO-Suc-AAPV-7-amino-4-methylcoumarylamide	Nonessential activation, V↑ α = 1, β = 5.5, KX = 1.2 mM	Früh (1996)
8	Myeloblastin Homo sapiens	3.4.21.76	Dermatan sulfate	MeO-Suc-AAPV-7-amino-4-methylcoumarylamide	Nonessential activation, V↑ α = 1, β = 5.3, KX = 0.13 mM	Früh (1996)
9	Myeloblastin Homo sapiens	3.4.21.76	GAGPS (5)	MeO-Suc-AAPV-7-amino-4-methylcoumarylamide	Nonessential activation, V↑ α = 1, β = 6.7, KX = 2.1 mM	Früh (1996)
10	Long-chain fatty acid omega-monooxygenase Homo sapiens	1.14.13.205	Dithiothreitol	Lauric acid	Wild type enzyme Activation, V↑ α = 1, β = 2.0 (6)	Albertolle (2017)
11	Long-chain fatty acid omega-monooxygenase Homo sapiens	1.14.13.205	Dithiothreitol	Lauric acid	F434S variant of the enzyme Activation, V↑ α = 1, β = 2.1 (6)	Albertolle (2017)
12	HtrA2 peptidase Homo sapiens	3.4.21.108	HAX-1 [Hematopoietic cell-specific protein 1 (HS1)-associated protein X-1]	Fluorescein isothiocyanate-labeled β-casein	V-system of allosteric modulation Activation: V↑, K0.5 unchanged Modifier binding cooperative (7)	Chaganti (2019)
13	Non-specific serine/ threonine protein kinase Species undeclared	2.7.11.1	Pyrvinium	α-Casein	Activation, V↑ (8)	Shen (2019)

⁽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 HSpA and HMx(Sp=Ca)I.

⁽⁵⁾ Glycosaminoglycan polysulfate: derived from chondroitin sulfate by additional sulfation (average of 3.25 sulfate groups per disaccharide unit).

⁽⁶⁾ Calculated from Figure 2. K_X could not be calculated from just one concentration of modifier (dithiothreitol = 1 mM), which is possibly a saturating concentration allowing the calculation of β as the ratio of the limiting rates in the presence and absence of modifier.

⁽⁷⁾ A clear demonstration of hyperbolic mixed, balanced activation. In the presence of HAX-1, the limiting rate increases, K_0.5 remains constant, and the specificity constant increases. In the absence of modifier the Hill coefficient is 2.4, and in its presence it is 1.9.

⁽⁸⁾ With just one modifier concentration, the value of K_X could not be measured, but the modifier mechanism is clearly hyperbolic mixed, balanced activation as deduced from the results presented in Fig. 4 and Table 1

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References

1. Albertolle ME, Kim D, Nagy LD, Yun C-H, Pozzi A, Savas Ü, Johnson EF, Guengerich FP (2017) Heme–thiolate sulfenylation of human cytochrome P450 4A11 functions as a redox switch for catalytic inhibition. J Biol Chem 292: 11230-11242. doi:10.1074/jbc.M117.792200
2. Chaganti LK, Dutta S, Kuppili RR, Mandal M, Bose K (2019) Structural modeling and role of HAX-1 as a positive allosteric modulator of human serine protease HtrA2. Biochem J 476: 2965-2980. doi:10.1042/bcj20190569
3. Früh H, Kostoulas G, Michel BA, Baici A (1996) Human myeloblastin (leukocyte proteinase 3): Reactions with substrates, inactivators and activators in comparison with leukocyte elastase. Biol Chem 377: 579-586. doi:10.1515/bchm3.1996.377.9.579
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.
5. Inagami T, Murachi T (1964) The mechanism of the specificity of trypsin catalysis. III. Activation of the catalytic site of trypsin by alkylammonium ions in the hydrolysis of acetylglycine ethyl ester. J Biol Chem 239: 1395-1401.
6. Inagami T, York SS (1968) Effect of alkyl guanidines and alkyl amines on trypsin catalysis. Biochemistry 7: 4045-4052. doi:10.1021/bi00851a036
7. Shen C, Li B, Astudillo L, Deutscher MP, Cobb MH, Capobianco AJ, Lee E, Robbins DJ (2019) The CK1α activator pyrvinium enhances the catalytic efficiency (kcat/Km) of CK1α. Biochemistry 58: 5102-5106. doi:10.1021/acs.biochem.9b00891