HSpI

Hyperbolic specific inhibition

Fingerprints of HSpI


#Enzyme
Species
EC no.ModifierSubstrate(1)Name given by authors (2)Reference(3)
1Acetylcholinesterase
Torpedo californica
3.1.1.7Propidium7-acetoxy-4-methyl-coumarinNonlinear competitive inhibition
α = 6.0, β = 1, KX = 1.2 μM
Berman
(1990)
2Cathepsin K
Homo sapiens
3.4.22.38Compound 6Cbz-Phe-Arg-7-amino-4-methyl-
coumarylamide
Hyperbolic competitive inhibition
α = 3.0, β = 1, KX = 270 μM
Novinec
(2014)
3Coagulation factor VIIa
Homo sapiens
3.4.21.21Peptide A-183
EEWEVLCWTWETCER
N-Methylsulfonyl-D-Phe-Gly-Arg-4-nitroanilide acetatePartial competitive inhibition
α = 2.2, β = 1, KX not calculable
Dennis
(2001)
4DNA helicase
Human papillomavirus 6 E1
3.6.4.12Bisphenylsulfonaceticacid derivative 4 (4)ATPHyperbolic competitive inhibition
α = 70, β = 1, KX = 190 μM
White
(2005)
5DNA helicase
Human papillomavirus 6 E1
3.6.4.12Bisphenylsulfonaceticacid derivative 6 (4)ATPHyperbolic competitive inhibition
α = 11, β = 1, KX = 26 μM
White
(2005)
6DNA helicase
Human papillomavirus 6 E1
3.6.4.12Bisphenylsulfonaceticacid derivative 7 (4)ATPHyperbolic competitive inhibition
α = 10, β = 1, KX = 35 μM
White
(2005)
7Thrombin
Homo sapiens
3.4.21.5Nα-acetyl desulfo
hirudin 45-65
Tos-Gly-Pro-Arg-p-nitroanilidePartially competitive inhibition
α = 4, β = 1, KX = 0.11 μM
DiMaio
(1990)
8Thrombin
Bos taurus
3.4.21.5Nα-acetyl desulfo
hirudin 45-65
Tos-Gly-Pro-Arg-p-nitroanilidePartially competitive inhibition
α = 2, β = 1, KX = 0.72 μM
DiMaio
(1990)
9NAD( P )H oxidase (5)
Mycobacterium tuberculosis
1.6.3.1NADoxNADredHyperbolic competitive inhibition
α = 6.2±1.7, β = 1, KX = 0.22 mM (6)
Worcel
(1965)
10Aldehyde dehydrogenase (NAD+)
Ovis aries
1.2.1.3Propionaldehyde4-Nitrophenylacetate
(esterase activity)
Partially competitive inhibition
α = 5.3, β = 1, KX = 1.44 μM
Blackwell
(1983)
11Ferredoxin-nitrite reductase
Chlamydomonas reinhardtii (7)
1.7.7.1NitrateNitritePartially competitive inhibition
α = 12.5, β = 1, KX = 2.7 μM
Córdoba
(1986)
12Receptor protein-tyrosine kinase
Homo sapiens
2.7.10.1RG 14467ATP(8)Hyperbolic competitive inhibition
α ≈ 4, β ≈ 1, KX ≤ 30 nM (8)
Hsu
(1991)
13Leukocyte elastase
Homo sapiens
3.4.21.37Heparin (17-19 kDa)Suc-Ala3-p-nitroanilideHyperbolic competitive inhibition
α = 3.5, β = 1, KX = 6.8 nM
(tight-binding)
Spencer
(2006)
14Purine nucleosidase
Trypanosoma vivax
3.2.2.2Dromedary antibody variable domain fragment (VHH 1602)p-nitrophenyl ribosideHyperbolic competitive inhibition
α = 2.9, β = 1, KX = 71 nM
Barlow
(2009)
15Pyruvate kinase
Homo sapiens
2.7.1.40L-PhenylalaninePhosphoenolpyruvateHyperbolic specific inhibition
α > 1, β ≈ 1, KX = 19 μM
Macpherson
(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 KX, 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, KX 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) Two experiments are reported in the paper. The values shown here refer to experiment 1.

(5) AMP-activated enzyme.

(6) The mechanism shown in Scheme 2 (p. 3406) lacks the closure of the thermodynamic cycle between E’S and IE’S, necessary for showing the linked functions.  α was calculated as K2‘/K1‘, the ratio of the apparent Michaelis constant at saturating [X] and Km in the absence of modifier, from the data below equation 10 on p. 3404.

(7) Wild type, strain 6145c.

(8) At fixed second substrate (K1), a peptide containing the major autophosphorylation site (Tyr-1173) of the epidermal growth factor receptor. Tight-binding (quasi irreversible) slow-onset inhibition; KX estimated by the authors. Approximate values of α and β were estimated from the data in Fig. 10.

References


  1. Barlow JN, Conrath K, Steyaert J (2009) Substrate-dependent modulation of enzyme activity by allosteric effector antibodies. Biochimica et Biophysica Acta – Proteins and Proteomics 1794: 1259-1268. doi:10.1016/j.bbapap.2009.03.019
  2. Berman HA, Leonard K (1990) Ligand exclusion on acetylcholinesterase. Biochemistry 29: 10640-10649. doi:10.1021/bi00499a010
  3. Blackwell LF, Bennett AF, Buckley PD (1983) Relationship between the mechanisms of the esterase and dehydrogenase activities of the cytoplasmic aldehyde dehydrogenase from sheep liver. An alternative view. Biochemistry 22: 3784-3791. doi:10.1021/bi00285a011
  4. Córdoba F, Cárdenas J, Fernández E (1986) Kinetic characterization of nitrite uptake and reduction by Chlamydomonas reinhardtii. Plant Physiol 82: 904-908. doi:10.1104/pp.82.4.904
  5. Dennis MS, Roberge M, Quan C, Lazarus RA (2001) Selection and characterization of a new class of peptide exosite inhibitors of coagulation factor VIIa. Biochemistry 40: 9513-9521. doi:10.1021/bi010591l
  6. DiMaio J, Gibbs B, Munn D, Lefebvre J, Ni F, Konishi Y (1990) Bifunctional thrombin inhibitors based on the sequence of hirudin45-65. J Biol Chem 265: 21698-21703. doi:10.1007/978-94-011-3034-9_321
  7. Hsu CY, Persons PE, Spada AP, Bednar RA, Levitzki A, Zilberstein A (1991) Kinetic analysis of the inhibition of the epidermal growth factor receptor tyrosine kinase by lavendustin-A and its analogue. J Biol Chem 266: 21105-21112.
  8. Macpherson JA, Theisen A, Masino L, Fets L, Driscoll PC, Encheva V, Snijders AP, Martin SR, Kleinjung J, Barran PE, Fraternali F, Anastasiou D (2019) Functional cross-talk between allosteric effects of activating and inhibiting ligands underlies PKM2 regulation. eLife 8: e45068. doi:10.7554/eLife.45068
  9. Novinec M, Lenarčič B, Baici A (2014) Probing the activity modification space of the cysteine peptidase cathepsin K with novel allosteric modifiers. PLoS One 9: e106642. doi:10.1371/journal.pone.0106642
  10. Spencer JL, Stone PJ, Nugent MA (2006) New insights into the inhibition of human neutrophil elastase by heparin. Biochemistry 45: 9104-9120. doi:10.1021/bi060338r
  11. White PW, Faucher AM, Massariol MJ, Welchner E, Rancourt J, Cartier M, Archambault J (2005) Biphenylsulfonacetic acid inhibitors of the human papillomavirus type 6 E1 helicase inhibit ATP hydrolysis by an allosteric mechanism involving tyrosine 486. Antimicrobial agents and chemotherapy 49: 4834-4842. doi:10.1128/AAC.49.12.4834-4842.2005
  12. Worcel A, Goldman DS, Cleland WW (1965) An allosteric reduced nicotinamide adenine dinucleotide oxidase from Mycobacterium tuberculosis. J Biol Chem 240: 3399-3407.