scholarly journals Tubulin-Tyrosine Ligase

2020 ◽  
Author(s):  
Keyword(s):  
Tubulin Tyrosine Ligase

scholarly journals Tubulin-tyrosine ligase catalyzes covalent binding of 3-fluoro-tyrosine to tubulin: kinetic and [19 F]NMR studies

FEBS Letters ◽  
1995 ◽  
Vol 374 (2) ◽  
pp. 165-168 ◽  
Author(s):  
Octavio Monasterio ◽  
Esteban Nova ◽  
Adamari López-Brauet ◽  
Rosalba Lagos
Keyword(s):  
Covalent Binding ◽  
Nmr Studies ◽  
Tubulin Tyrosine Ligase ◽  
19 F Nmr

Suppression of tubulin tyrosine ligase during tumor growth

1998 ◽  
Vol 111 (2) ◽  
pp. 171-181 ◽  
Author(s):  
L. Lafanechere ◽  
C. Courtay-Cahen ◽  
T. Kawakami ◽  
M. Jacrot ◽  
M. Rudiger ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Selection Process ◽  
Eukaryotic Cells ◽  
C Terminus ◽  
Tubulin Isotype ◽  
Clonal Cell Lines ◽  
Tubulin Tyrosine Ligase ◽  
Nih 3T3 ◽  
Tubulin Carboxypeptidase

The C terminus of the tubulin alpha-subunit of most eukaryotic cells undergoes a cycle of tyrosination and detyrosination using two specific enzymes, a tubulin tyrosine ligase (TTL) and a tubulin carboxypeptidase. Although this enzyme cycle is conserved in evolution and exhibits rapid turnover, the meaning of this modification has remained elusive. We have isolated several NIH-3T3 derived clonal cell lines that lack TTL (TTL-). TTL- cells contain a unique tubulin isotype (delta2-tubulin) that can be detected with specific antibodies. When injected into nude mice, both TTL- cells and TTL- cells stably transfected with TTL cDNA form sarcomas. But in tumors formed from TTL rescued cells, TTL is systematically lost during tumor growth. A strong selection process has thus acted during tumor growth to suppress TTL activity. In accord with this result, we find suppression of TTL activity in the majority of human tumors assayed with delta2-tubulin antibody. We conclude there is a widespread loss of TTL activity during tumor growth in situ, suggesting that TTL activity may play a role in tumor cell regulation.

The Structure of MT189-Tubulin Complex Provides Insights into Drug Design

2019 ◽  
Vol 16 (9) ◽  
pp. 1069-1073
Author(s):  
Zhongping Li ◽  
Lingling Ma ◽  
Chengyong Wu ◽  
Tao Meng ◽  
Lanping Ma ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Binding Site ◽  
Complex Structure ◽  
Microtubule Assembly ◽  
Tubulin Polymerization ◽  
Colchicine Binding Site ◽  
Structure Activity ◽  
Tubulin Tyrosine Ligase ◽  
Tubulin Polymerization Inhibitors

Background: Drugs that interfere with microtubule dynamics are used widely in cancer chemotherapy. Microtubules are composed of αβ-tubulin heterodimers, and the colchicine binding site of tubulin is an important pocket for designing tubulin polymerization inhibitors. We have previously designed and synthesized a series of colchicine binding site inhibitors (CBSIs). However, these compounds showed no anticancer activity in vivo. Then, we have used a deconstruction approach to obtain a new derivative MT189, which showed in vivo anticancer activity. Methods: We crystallized a protein complex including two tubulins, one stathmin-like domain of RB3 and one tubulin tyrosine ligase, and soaked MT189 into the crystals. We collected the diffraction data and determined the tubulin-MT189 structure to 2.8 Å. Results: Here, we report the crystal structure of tubulin complexed with MT189, elucidate how the small-molecular agent binds to tubulin and inhibits microtubule assembly, and explain previous results of the structure-activity-relationship studies. Conclusion: The tubulin-MT189 complex structure reveals the interactions between this agent and tubulin and provides insights into the design of new derivatives targeting the colchicine binding site.

scholarly journals Structural basis of tubulin tyrosination by tubulin tyrosine ligase

2013 ◽  
Vol 200 (3) ◽  
pp. 259-270 ◽  
Author(s):  
Andrea E. Prota ◽  
Maria M. Magiera ◽  
Marijn Kuijpers ◽  
Katja Bargsten ◽  
Daniel Frey ◽  
...  
Keyword(s):  
Neuronal Development ◽  
Structural Basis ◽  
Tubulin Dimer ◽  
Cellular Assays ◽  
Molecular Mechanism Of Action ◽  
Tubulin Tyrosine Ligase ◽  
Modified Forms ◽  
Tubulin Structure ◽  
Β Tubulin

Tubulin tyrosine ligase (TTL) catalyzes the post-translational retyrosination of detyrosinated α-tubulin. Despite the indispensable role of TTL in cell and organism development, its molecular mechanism of action is poorly understood. By solving crystal structures of TTL in complex with tubulin, we here demonstrate that TTL binds to the α and β subunits of tubulin and recognizes the curved conformation of the dimer. Biochemical and cellular assays revealed that specific tubulin dimer recognition controls the activity of the enzyme, and as a consequence, neuronal development. The TTL–tubulin structure further illustrates how the enzyme binds the functionally crucial C-terminal tail sequence of α-tubulin and how this interaction catalyzes the tyrosination reaction. It also reveals how TTL discriminates between α- and β-tubulin, and between different post-translationally modified forms of α-tubulin. Together, our data suggest that TTL has specifically evolved to recognize and modify tubulin, thus highlighting a fundamental role of the evolutionary conserved tubulin tyrosination cycle in regulating the microtubule cytoskeleton.

scholarly journals Tubulin Tyrosine Ligase and Stathmin Compete for Tubulin Binding In Vitro

2013 ◽  
Vol 425 (14) ◽  
pp. 2412-2414 ◽  
Author(s):  
Agnieszka Szyk ◽  
Grzegorz Piszczek ◽  
Antonina Roll-Mecak
Keyword(s):  
Tubulin Binding ◽  
Tubulin Tyrosine Ligase
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