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6VZU

TTLL6 bound to alpha-elongation analog

Summary for 6VZU
Entry DOI10.2210/pdb6vzu/pdb
DescriptorTubulin polyglutamylase TTLL6, TTLL6 unregistered chain, GLYCEROL, ... (10 entities in total)
Functional Keywordsttll6, glutamylase, amino-acid ligase, phosphinic acid inhibitors, ligase
Biological sourceMus musculus (Mouse)
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Total number of polymer chains6
Total formula weight221446.40
Authors
Mahalingan, K.K.,Keenen, E.K.,Strickland, M.,Li, Y.,Liu, Y.,Ball, H.B.,Tanner, M.E.,Tjandra, N.,Roll-Mecak, A. (deposition date: 2020-02-28, release date: 2020-08-12, Last modification date: 2023-10-11)
Primary citationMahalingan, K.K.,Keith Keenan, E.,Strickland, M.,Li, Y.,Liu, Y.,Ball, H.L.,Tanner, M.E.,Tjandra, N.,Roll-Mecak, A.
Structural basis for polyglutamate chain initiation and elongation by TTLL family enzymes.
Nat.Struct.Mol.Biol., 27:802-813, 2020
Cited by
PubMed Abstract: Glutamylation, introduced by tubulin tyrosine ligase-like (TTLL) enzymes, is the most abundant modification of brain tubulin. Essential effector proteins read the tubulin glutamylation pattern, and its misregulation causes neurodegeneration. TTLL glutamylases post-translationally add glutamates to internal glutamates in tubulin carboxy-terminal tails (branch initiation, through an isopeptide bond), and additional glutamates can extend these (elongation). TTLLs are thought to specialize in initiation or elongation, but the mechanistic basis for regioselectivity is unknown. We present cocrystal structures of murine TTLL6 bound to tetrahedral intermediate analogs that delineate key active-site residues that make this enzyme an elongase. We show that TTLL4 is exclusively an initiase and, through combined structural and phylogenetic analyses, engineer TTLL6 into a branch-initiating enzyme. TTLL glycylases add glycines post-translationally to internal glutamates, and we find that the same active-site residues discriminate between initiase and elongase glycylases. These active-site specializations of TTLL glutamylases and glycylases ultimately yield the chemical complexity of cellular microtubules.
PubMed: 32747782
DOI: 10.1038/s41594-020-0462-0
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (1.98 Å)
Structure validation

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