PDBsum entry 4bkx

Transcription

PDB id: 4bkx

Contents

Protein chains

161 a.a.

369 a.a.

Ligands

ACT

SO4 ×4

Metals

_ZN

__K ×2

PDB id:

4bkx

Name:

Transcription

Title:

The structure of hdac1 in complex with the dimeric elm2-sant domain of mta1 from the nurd complex

Structure:

Metastasis-associated protein mta1. Chain: a. Fragment: elm2-sant. Engineered: yes. Histone deacetylase 1. Chain: b. Synonym: hd1. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: homo sapiens. Expression_system_taxid: 9606. Expression_system_cell_line: hek293f.

Resolution:

3.00Å R-factor: 0.213 R-free: 0.261

Authors:

C.J.Millard,P.J.Watson,I.Celardo,Y.Gordiyenko,S.M.Cowley, C.V.Robinson,L.Fairall,J.W.R.Schwabe

Key ref:

C.J.Millard et al. (2013). Class I HDACs share a common mechanism of regulation by inositol phosphates. Mol Cell, 51, 57-67. PubMed id: 23791785 DOI: 10.1016/j.molcel.2013.05.020

Date:

30-Apr-13 Release date: 03-Jul-13

Protein chain

Q13330  (MTA1_HUMAN) -  Metastasis-associated protein MTA1 from Homo sapiens

Seq: 715 a.a.

Struc: 161 a.a.

Protein chain

Q13547  (HDAC1_HUMAN) -  Histone deacetylase 1 from Homo sapiens

Seq: 482 a.a.

Struc: 369 a.a.

Enzyme reactions

• Enzyme class 1: Chain B: E.C.3.5.1.- - ?????
• Enzyme class 2: Chain B: E.C.3.5.1.98 - histone deacetylase.
• Reaction: N₆-acetyl-L-lysyl-[histone] + H2O = L-lysyl-[histone] + acetate

N(6)-acetyl-L-lysyl-[histone] + H2O = L-lysyl-[histone] (Bound ligand (Het Group name = ACT) corresponds exactly) + acetate

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

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

Key reference

DOI no: 10.1016/j.molcel.2013.05.020

Mol Cell 51:57-67 (2013)

PubMed id: 23791785

Class I HDACs share a common mechanism of regulation by inositol phosphates.

C.J.Millard, P.J.Watson, I.Celardo, Y.Gordiyenko, S.M.Cowley, C.V.Robinson, L.Fairall, J.W.Schwabe.

ABSTRACT

Class I histone deacetylases (HDAC1, HDAC2, and HDAC3) are recruited by cognate corepressor proteins into specific transcriptional repression complexes that target HDAC activity to chromatin resulting in chromatin condensation and transcriptional silencing. We previously reported the structure of HDAC3 in complex with the SMRT corepressor. This structure revealed the presence of inositol-tetraphosphate [Ins(1,4,5,6)P4] at the interface of the two proteins. It was previously unclear whether the role of Ins(1,4,5,6)P4 is to act as a structural cofactor or a regulator of HDAC3 activity. Here we report the structure of HDAC1 in complex with MTA1 from the NuRD complex. The ELM2-SANT domains from MTA1 wrap completely around HDAC1 occupying both sides of the active site such that the adjacent BAH domain is ideally positioned to recruit nucleosomes to the active site of the enzyme. Functional assays of both the HDAC1 and HDAC3 complexes reveal that Ins(1,4,5,6)P4 is a bona fide conserved regulator of class I HDAC complexes.