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Literature summary for 6.3.2.25 extracted from

  • Prota, A.E.; Magiera, M.M.; Kuijpers, M.; Bargsten, K.; Frey, D.; Wieser, M.; Jaussi, R.; Hoogenraad, C.C.; Kammerer, R.A.; Janke, C.; Steinmetz, M.O.
    Structural basis of tubulin tyrosination by tubulin tyrosine ligase (2013), J. Cell Biol., 200, 259-270.
    View publication on PubMedView publication on EuropePMC
Search for more literature for 6.3.2.25

Crystallization (Commentary)

Crystallization (Comment) Organism
purified enzyme in complex with alpha- and beta-tubulin heterodimers, X-ray diffraction structure determination and analysis Gallus gallus

Protein Variants

Protein Variants Comment Organism
E331Q site-directed mutagenesis, catalytically inactive mutant Gallus gallus
H54A site-directed mutagenesis, the mutant enzyme shows moderately reduced binding to tubulin dimers Gallus gallus
R36E site-directed mutagenesis, the mutant enzyme shows strongly reduced binding to tubulin dimers Gallus gallus
R51A site-directed mutagenesis, the mutant enzyme shows moderately reduced binding to tubulin dimers Gallus gallus
R51A/H54A site-directed mutagenesis, the mutant enzyme shows strongly reduced binding to tubulin dimers Gallus gallus
R66E site-directed mutagenesis, the mutant enzyme shows strongly reduced binding to tubulin dimers Gallus gallus
S152E site-directed mutagenesis, the mutant shows over 90% reduced activity compared to the wild-type enzyme Gallus gallus
S76E site-directed mutagenesis, the mutant is comparable to the wild-type enzyme Gallus gallus

Metals/Ions

Metals/Ions Comment Organism Structure
Mg2+ required Mus musculus
Mg2+ required Gallus gallus

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
ATP + detyrosinated alpha-tubulin + L-tyrosine Mus musculus
-
 alpha-tubulin + ADP + phosphate
-
 ?
ATP + detyrosinated alpha-tubulin + L-tyrosine Gallus gallus tubuline alpha/beta-dimers, no activity with tyrosinate polymerized microtubules in which the tubulin subunits adopt a straighter configuration alpha-tubulin + ADP + phosphate
-
 ?

Organism

Organism UniProt Comment Textmining
Gallus gallus E1BQ43
-
-
Mus musculus
-
-
-

Posttranslational Modification

Posttranslational Modification Comment Organism
phosphoprotein phosphorylation of Ser152 might play an important role in the regulation of tubulin tyrosine ligase activity Gallus gallus

Reaction

Reaction Comment Organism Reaction ID
ATP + detyrosinated alpha-tubulin + L-tyrosine = alpha-tubulin + ADP + phosphate reaction mechanism, structure-function analysis, overview Gallus gallus
a

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
ATP + detyrosinated alpha-tubulin + L-tyrosine
-
 Mus musculus alpha-tubulin + ADP + phosphate
-
 ?
ATP + detyrosinated alpha-tubulin + L-tyrosine
-
 Gallus gallus alpha-tubulin + ADP + phosphate
-
 ?
ATP + detyrosinated alpha-tubulin + L-tyrosine tubuline alpha/beta-dimers, no activity with tyrosinate polymerized microtubules in which the tubulin subunits adopt a straighter configuration Gallus gallus alpha-tubulin + ADP + phosphate
-
 ?

Synonyms

Synonyms Comment Organism
TTL
-
 Mus musculus
TTL
-
 Gallus gallus
tubulin tyrosine ligase
-
 Mus musculus
tubulin tyrosine ligase
-
 Gallus gallus

Cofactor

Cofactor Comment Organism Structure
ATP
-
 Mus musculus
ATP
-
 Gallus gallus

General Information

General Information Comment Organism
malfunction mutation of tubulin binding residues largely abolishes the enzyme ability to tyrosinate alpha-tubulin and restrict neurite outgrowth in cultured neurons. The neuronal defects of tubulin tyrosine ligase knockout mice are due to the loss of tubulin tyrosination and not because the enzyme is required to tyrosinate any other substrates. Neurons from TTL-null mice show strong developmental defects, including increased neurite extensions and premature differentiation Mus musculus
additional information the enzyme's tubulin-contacting residues are well conserved. The alpha-tubulin residues alphaGlu441 and alphaGlu449 anchor the tail by forming hydrogen bonds with residues Arg73, Ala75, Ser76, Ser152, and Val179, and Asn10, Ser12, Arg44, and Pro336 of TTL, respectively. When bound to the enzyme, the polypeptide chain of the alpha-tubulin tail adopts a loop-like conformation between the tail-anchoring residues alphaGlu441 and alphaGlu449. The enzyme's orientation on tubulin heterodimers places its catalytic domain near to alpha-tubulin's C-terminal tail, which binds to the enzyme's active site through two glutamate residues missing from beta-tubulin's C-terminus Gallus gallus
physiological function the enzyme specifically recognizes the C-terminus of alpha-tubulin adding L-tyrosine to modulate the behavior of microtubules, tyrosinated microtubules are more dynamic than detyrosinated filaments in cells. The enzyme is bound at the interface of tubulin alpha- and beta-subunits and specifically recognizes the tubulin dimer's curved conformation Mus musculus
physiological function the enzyme specifically recognizes the C-terminus of alpha-tubulin adding L-tyrosine to modulate the behavior of microtubules, tyrosinated microtubules are more dynamic than detyrosinated filaments in cells. The enzyme is bound at the interface of tubulin alpha- and beta-subunits and specifically recognizes the tubulin dimer's curved conformation Gallus gallus