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Literature summary for 3.6.5.6 extracted from

  • Bailey, M.E.; Jiang, N.; Dima, R.I.; Ross, J.L.
    Microtubule severing enzymes couple ATPase activity with tubulin GTPase spring loading (2016), Biopolymers, 105, 547-556 .
    View publication on PubMed
Search for more literature for 3.6.5.6

Inhibitors

Inhibitors Comment Organism Structure
Colchicine a small molecule inhibitor that binds to tubulin dimers rendering them unable to incorporate into filaments. It does not destabilize actively, but rather inhibit repolymerization after regular depolymerization Homo sapiens
additional information a class of destabilizers consists of the microtubule-severing enzymes from the ATPases associated with various cellular activities (AAA+) family of ATP-enzymes. GTP-driven microtubule dynamics are coupled to ATP-driven destabilization by severing enzymes, examples and mechanism, detailed overview Homo sapiens
vinblastine a small molecule inhibitor that binds to tubulin dimers rendering them unable to incorporate into filaments. It does not destabilize actively, but rather inhibit repolymerization after regular depolymerization Homo sapiens

Localization

Localization Comment Organism GeneOntology No. Textmining
microtubule
-
 Homo sapiens 5874
-

Metals/Ions

Metals/Ions Comment Organism Structure
Ca2+ calcium apparently competes for the magnesium binding site at the E-site to cause rapid hydrolysis of GTP to GDP Homo sapiens
Mg2+ required Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
GTP + H2O Homo sapiens
-
 GDP + phosphate
-
 ?

Organism

Organism UniProt Comment Textmining
Homo sapiens P23258 tubulin gamma-1 chain
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
GTP + H2O
-
 Homo sapiens GDP + phosphate
-
 ?
additional information GTP binding to the alpha occurs in the dimerization region between the alpha and beta monomers and remains unhydrolyzed. This is called the non-exchangeable site or N-site. GTP binding to beta-tubulin sits at the interface between two dimers within the protofilament, the longitudinal lattice of tubulin dimers running parallel to the microtubule filament long axis. Tubulin controls microtubule dynamics, analysis of GTP hydrolysis on reconstructed microtubules, mechanism, overview. GTP binding to the beta tubulin is hydrolyzable and this site is called the exchangeable site or E-site. Hydrolysis of GTP at the E-site is required for microtubule dynamic instability. GTP hydrolysis leads to the compaction of the lattice around the interdimer longitudinal interface sandwiching the E-site nucleotide. This compaction in turn results in a conformational rearrangement in all alpha-tubulin monomers corresponding to a small rotation of the intermediate domain and C-terminal H11-H12 helices with respect to the N-terminal domain in alpha-tubulin. Additionally, helix H8 from alpha-tubulin is also distorted in the GDP-state. The hydrolysis is immediate, but the probability of hydrolysis within a certain time is increased when the next dimer binds. Such catalysis leads to a situation where dimers at the end of the filament typically have GTP, and are in a non-compacted, straight conformation. This is called the GTP cap. Dimers within the body of the filament are typically in the GDP-state and prefer to be in the compacted, bent conformation. Due to binding to neighbors, the GDP dimers cannot compact and are held straight. Thus, GDP dimers in the body are in a high potential energy state, spring-loaded to compact whenever constraints are relaxed. The purpose of the GTPase is to force dimers within the body into this spring-loaded state. When the dimers at the top are lost or hydrolyzed stochastically, the end cap loses coherence and the entire microtubule bends back to relax the dimers to their lowest energy state. The longitudinal binding is less affected by the hydrolysis and protofilaments peel back into rings unraveling the microtubule Homo sapiens ?
-
-

Subunits

Subunits Comment Organism
heterodimer tubulin comes as a heterodimer of alpha and beta forms While there is only 45% amino-acid sequence similarity between alpha and beta tubulin isoforms, the three-dimensional structures of the monomers are very similar, each consisting of three domains of similar length and secondary structure composition: the N-terminal, the middle, and the C-terminal domain Homo sapiens

Synonyms

Synonyms Comment Organism
GTPase
-
 Homo sapiens
tubulin
-
 Homo sapiens

General Information

General Information Comment Organism
evolution tubulin comes as a heterodimer of alpha and beta forms While there is only 45% amino-acid sequence similarity between alpha and beta tubulin isoforms, the three-dimensional structures of the monomers are very similar, each consisting of three domains of similar length and secondary structure composition: the N-terminal, the middle, and the C-terminal domain. Both alpha and beta bind GTP Homo sapiens
physiological function microtubules are amazing filaments made of GTPase enzymes that store energy used for their own selfdestruction to cause a stochastically driven dynamic called dynamic instability. Dynamic instability can be reproduced in vitro with purified tubulin, but the dynamics do not mimic that observed in cells. This is because stabilizers, e.g. paclitaxel, and destabilizers, e.g. Ca2+, act to alter microtubule dynamics. Another class of destabilizers consists of the microtubule-severing enzymes from the ATPases associated with various cellular activities (AAA+) family of ATP-enzymes. GTP-driven microtubule dynamics are coupled to ATP-driven destabilization by severing enzymes. The GTP enzyme that polymerizes into the microtubules is called tubulin, which comes as a heterodimer of alpha and beta forms. Tubulin controls microtubule dynamics, analysis of GTP hydrolysis on reconstructed microtubules, mechanism, overview Homo sapiens