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Literature summary for 2.3.2.26 extracted from

  • Todaro, D.R.; Augustus-Wallace, A.C.; Klein, J.M.; Haas, A.L.
    Oligomerization of the HECT ubiquitin ligase NEDD4-2/NEDD4L is essential for polyubiquitin chain assembly (2018), J. Biol. Chem., 293, 18192-18206 .
    View publication on PubMedView publication on EuropePMC
Search for more literature for 2.3.2.26

Cloned(Commentary)

Cloned (Comment) Organism
codon-optimized expression in Escherichia coli Homo sapiens

Protein Variants

Protein Variants Comment Organism
C922A dominant-negative active site mutant, predicted to result in an end point of 33% activity compared with wild-type. Addition of mutant C922A to the wild-type enzyme at saturating concentration inhibits wild-type NEDD4L to 30% limiting activity Homo sapiens
E646A 400fold reduction in kcat value for polyubiquitination Homo sapiens
E646D 1200fold reduction in kcat value for polyubiquitination Homo sapiens
F823A 10000fold reduction in kcat value Homo sapiens
F823D no detectable free or anchored polyubiquitin chain assembly is observed with the mutant Homo sapiens
R604D 15fold reduction in kcat value for polyubiquitination Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
N-acetylphenylalanylamide i.e. Phe-823 mimic, acts as a noncompetitive inhibitor of polyubiquitin chain elongation by destabilizing the active trimer Homo sapiens

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
0.0046
-
 [Ubc5B]-L-lysine mutant E646D, pH 7.5, 37°C Homo sapiens
0.0053
-
 [Ubc5B]-L-lysine mutant R604A, pH 7.5, 37°C Homo sapiens
0.011
-
 [Ubc5B]-L-lysine mutant E646A, pH 7.5, 37°C Homo sapiens
0.036
-
 [Ubc5B]-L-lysine mutant F823A, pH 7.5, 37°C Homo sapiens
0.037
-
 [Ubc5B]-L-lysine wild-type, pH 7.5, 37°C Homo sapiens

Molecular Weight [Da]

Molecular Weight [Da] Molecular Weight Maximum [Da] Comment Organism
190000
-
 gel filtration Homo sapiens
290000
-
 dynamic light scattering Homo sapiens
330000
-
 dynamic light scattering, reoligomnerization of 80-kDa species Homo sapiens

Organism

Organism UniProt Comment Textmining
Homo sapiens
-
-
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
[HECT-E3-ubiquitin-carrier protein NEDD4L]-S-ubiquitin-L-cysteine + [Ubc5B]-L-lysine
-
 Homo sapiens [HECT-E3-ubiquitin-carrier protein NEDD4]-L-cysteine + [Ubc5B]-N6-ubiquinyl-L-lysine
-
 ?

Subunits

Subunits Comment Organism
More the predicted intersubunit interface has an absolutely conserved residue Phe823, substitution of which destabilizes the trimer and results in an over 10000fold decrease in kcat for polyubiquitin chain assembly Homo sapiens
trimer 3 * 80000, gel filtration Homo sapiens

Synonyms

Synonyms Comment Organism
Nedd4L
-
 Homo sapiens

Turnover Number [1/s]

Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
0.000009
-
 [Ubc5B]-L-lysine mutant F823A, pH 7.5, 37°C Homo sapiens
0.00001
-
 [Ubc5B]-L-lysine mutant E646D, pH 7.5, 37°C Homo sapiens
0.000029
-
 [Ubc5B]-L-lysine mutant E646A, pH 7.5, 37°C Homo sapiens
0.000083
-
 [Ubc5B]-L-lysine mutant R604A, pH 7.5, 37°C Homo sapiens
0.012
-
 [Ubc5B]-L-lysine wild-type, pH 7.5, 37°C Homo sapiens

Ki Value [mM]

Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
8
-
 N-acetylphenylalanylamide wild-type, pH 7.5, 37°C Homo sapiens

General Information

General Information Comment Organism
physiological function monomeric NEDD4L catalyzes only HECT ubiquitin thioester formation and monoubiquitination, whereas polyubiquitin chain assembly requires NEDD4L oligomerization and sites 1 and 2 to function in trans Homo sapiens