Tubulin tyrosine ligase (TTL)

Tubulin tyrosine ligase (TTL) is an enzyme in the ATP-grasp superfamily that catalyzes the C-terminal tyrosination of α-tubulin in most eukaryotic cells. This posttranslational modification is critical for microtubule stability and interactions with microtubule-associated proteins. TTL uses a bipartite substrate recognition mechanism to bind tubulin, capping the tubulin dimer and preventing its incorporation into microtubules, thereby regulating the balance of monomeric and polymeric tubulin inside cells. Loss or suppression of TTL activity leads to morphogenic defects, impaired neuronal network formation and is associated with increased cancer cell invasiveness and poor clinical prognosis. TTL itself is essential, and its absence results in perinatal lethality in mice due to failed neural development. While TTL is structurally related to other tubulin-modifying enzymes, its biophysical mechanism is unique and may represent a future target for tumor metastasis prevention and microtubule dynamics modulation[1][2].

Other names

Tubulin--tyrosine ligaseTTLtubulin--tyrosine ligaseMGC462352410003M22Rik

For prospective drugs: Inhibition or activation of TTL could affect tubulin tyrosination, altering microtubule dynamics and impacting cell division, migration, and tumor cell reattachment[1].