PDBsum entry 5g0h

Cell cycle

PDB id: 5g0h

Contents

Protein chain

360 a.a.

Ligands

E1Z

EDO ×10

Metals

__K ×2

_ZN

Waters ×353

PDB id:

5g0h

Name:

Cell cycle

Title:

Crystal structure of danio rerio hdac6 cd2 in complex with (s)- trichostatin a

Structure:

Hdac6. Chain: a. Fragment: catalytic domain 2, unp residues 40-831. Engineered: yes

Source:

Danio rerio. Zebrafish. Organism_taxid: 7955. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Expression_system_cell_line: sf9.

Resolution:

1.60Å R-factor: 0.152 R-free: 0.174

Authors:

Y.Miyake,J.J.Keusch,L.Wang,M.Saito,D.Hess,X.Wang,B.J.Melancon, P.Helquist,H.Gut,P.Matthias

Key ref:

Y.Miyake et al. (2016). Structural insights into HDAC6 tubulin deacetylation and its selective inhibition. Nat Chem Biol, 12, 748-754. PubMed id: 27454931 DOI: 10.1038/nchembio.2140

Date:

18-Mar-16 Release date: 27-Jul-16

Protein chain

F8W4B7  (F8W4B7_DANRE) -  Protein deacetylase HDAC6 from Danio rerio

Seq: 1081 a.a.

Struc: 360 a.a.

DOI no: 10.1038/nchembio.2140

Nat Chem Biol 12:748-754 (2016)

PubMed id: 27454931

Structural insights into HDAC6 tubulin deacetylation and its selective inhibition.

Y.Miyake, J.J.Keusch, L.Wang, M.Saito, D.Hess, X.Wang, B.J.Melancon, P.Helquist, H.Gut, P.Matthias.

ABSTRACT

We report crystal structures of zebrafish histone deacetylase 6 (HDAC6) catalytic domains in tandem or as single domains in complex with the (R) and (S) enantiomers of trichostatin A (TSA) or with the HDAC6-specific inhibitor nexturastat A. The tandem domains formed, together with the inter-domain linker, an ellipsoid-shaped complex with pseudo-twofold symmetry. We identified important active site differences between both catalytic domains and revealed the binding mode of HDAC6 selective inhibitors. HDAC inhibition assays with (R)- and (S)-TSA showed that (R)-TSA was a broad-range inhibitor, whereas (S)-TSA had moderate selectivity for HDAC6. We identified a uniquely positioned α-helix and a flexible tryptophan residue in the loop joining α-helices H20 to H21 as critical for deacetylation of the physiologic substrate tubulin. Using single-molecule measurements and biochemical assays we demonstrated that HDAC6 catalytic domain 2 deacetylated α-tubulin lysine 40 in the lumen of microtubules, but that its preferred substrate was unpolymerized tubulin.