PDBsum entry 4h6u

Transferase

PDB id: 4h6u

Contents

Protein chains

165 a.a.

161 a.a.

Ligands

ACO ×2

PO4

Metals

__K

Waters ×41

PDB id:

4h6u

Name:

Transferase

Title:

Tubulin acetyltransferase mutant

Structure:

Alpha-tubulin n-acetyltransferase. Chain: a, b. Synonym: alpha-tat, tat, acetyltransferase mec-17 homolog. Engineered: yes. Mutation: yes

Source:

Danio rerio. Leopard danio,zebra danio,zebra fish. Organism_taxid: 7955. Gene: atat1, mec17, si:ch211-152p11.5, zgc:65893. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

2.45Å R-factor: 0.199 R-free: 0.248

Authors:

A.Roll-Mecak,V.Kizub,A.Szyk

Key ref:

V.Kormendi et al. (2012). Crystal structures of tubulin acetyltransferase reveal a conserved catalytic core and the plasticity of the essential N terminus. J Biol Chem, 287, 41569-41575. PubMed id: 23105108

Date:

19-Sep-12 Release date: 07-Nov-12

Protein chain

Q6PH17  (ATAT_DANRE) -  Alpha-tubulin N-acetyltransferase 1 from Danio rerio

Seq: 297 a.a.

Struc: 165 a.a.*

Protein chain

Q6PH17  (ATAT_DANRE) -  Alpha-tubulin N-acetyltransferase 1 from Danio rerio

Seq: 297 a.a.

Struc: 161 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

Enzyme reactions

• Enzyme class: Chains A, B: E.C.2.3.1.108 - alpha-tubulin N-acetyltransferase.
• Reaction: L-lysyl-[alpha-tubulin] + acetyl-CoA = N₆-acetyl-L-lysyl-[alpha- tubulin] + CoA + H⁺

L-lysyl-[alpha-tubulin] (Bound ligand (Het Group name = ACO) corresponds exactly) + acetyl-CoA = N(6)-acetyl-L-lysyl-[alpha- tubulin] + CoA + H(+)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Added reference

J Biol Chem 287:41569-41575 (2012)

PubMed id: 23105108

Crystal structures of tubulin acetyltransferase reveal a conserved catalytic core and the plasticity of the essential N terminus.

V.Kormendi, A.Szyk, G.Piszczek, A.Roll-Mecak.

ABSTRACT

Tubulin acetyltransferase (TAT) acetylates Lys-40 of α-tubulin in the microtubule lumen. TAT is inefficient, and its activity is enhanced when tubulin is incorporated in microtubules. Acetylation is associated with stable microtubules and regulates the binding of microtubule motors and associated proteins. TAT is important in neuronal polarity and mechanosensation, and decreased tubulin acetylation levels are associated with axonal transport defects and neurodegeneration. We present the first structure of TAT in complex with acetyl-CoA (Ac-CoA) at 2.7 Å resolution. The structure reveals a conserved stable catalytic core shared with other GCN5 superfamily acetyltransferases consisting of a central β-sheet flanked by α-helices and a C-terminal β-hairpin unique to TAT. Structure-guided mutagenesis establishes the molecular determinants for Ac-CoA and tubulin substrate recognition. The wild-type TAT construct is a monomer in solution. We identify a metastable interface between the conserved core and N-terminal domain that modulates the oligomerization of TAT in solution and is essential for activity. The 2.45 Å resolution structure of an inactive TAT construct with an active site point mutation near this interface reveals a domain-swapped dimer in which the functionally essential N terminus shows evidence of marked structural plasticity. The sequence segment corresponding to this structurally plastic region in TAT has been implicated in substrate recognition in other GCN5 superfamily acetyltransferases. Our structures provide a rational platform for the mechanistic dissection of TAT activity and the design of TAT inhibitors with therapeutic potential in neuronal regeneration.