1ZZ3

Crystal structure of a HDAC-like protein with CypX bound


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.76 Å
  • R-Value Free: 0.191 
  • R-Value Work: 0.156 
  • R-Value Observed: 0.158 

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This is version 1.3 of the entry. See complete history


Literature

Crystal structure of a bacterial class 2 histone deacetylase homologue

Nielsen, T.K.Hildmann, C.Dickmanns, A.Schwienhorst, A.Ficner, R.

(2005) J Mol Biol 354: 107-120

  • DOI: https://doi.org/10.1016/j.jmb.2005.09.065
  • Primary Citation of Related Structures:  
    1ZZ0, 1ZZ1, 1ZZ3

  • PubMed Abstract: 

    Histone deacetylases (HDACs) are among the most promising targets in cancer therapy. However, structural information greatly enhancing the design of HDAC inhibitors as novel chemotherapeutics has not been available on class 2 HDACs so far. Here we present the structure of the bacterial FB188 HDAH (histone deacetylase-like amidohydrolase from Bordetella/Alcaligenes strain FB188) that reveals high sequential and functional homology to human class 2 HDACs. FB188 HDAH is capable to remove the acetyl moiety from acetylated histones. Several HDAC-specific inhibitors, which have been shown to inhibit tumor activity in both pre-clinical models and in clinical trials, also inhibit FB188 HDAH. We have determined the crystal structure of FB188 HDAH at a resolution of 1.6 angstroms in complex with the reaction product acetate, as well as in complex with the inhibitors suberoylanilide hydroxamic acid (SAHA) and cyclopentyle-propionyle hydroxamic acid (CypX) at a resolution of 1.57 angstroms and 1.75 angstroms, respectively. FB188 HDAH exhibits the canonical fold of class 1 HDACs and contains a catalytic zinc ion. The highest structural diversity compared to class 1 enzymes is found in loop regions especially in the area around the entrance of the active site, indicating significant differences among the acetylated proteins binding to class 1 and 2 HDACs, respectively.


  • Organizational Affiliation

    Abteilung für Molekulare Strukturbiologie, Institut für Mikrobiologie und Genetik und GZMB, Justus-von-Liebig Weg 11, 37077 Göttingen, Germany.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Histone deacetylase-like amidohydrolase
A, B, C, D
369Alcaligenaceae bacterium FB188Mutation(s): 0 
EC: 3.5.1
UniProt
Find proteins for Q70I53 (Alcaligenes sp. (strain DSM 11172))
Explore Q70I53 
Go to UniProtKB:  Q70I53
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ70I53
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
3YP
Query on 3YP

Download Ideal Coordinates CCD File 
E [auth A],
I [auth B],
M [auth C],
Q [auth D]
3-CYCLOPENTYL-N-HYDROXYPROPANAMIDE
C8 H15 N O2
PCDWXHSMVLWAMG-UHFFFAOYSA-N
ZN
Query on ZN

Download Ideal Coordinates CCD File 
F [auth A],
J [auth B],
N [auth C],
R [auth D]
ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
K
Query on K

Download Ideal Coordinates CCD File 
G [auth A]
H [auth A]
K [auth B]
L [auth B]
O [auth C]
G [auth A],
H [auth A],
K [auth B],
L [auth B],
O [auth C],
P [auth C],
S [auth D],
T [auth D]
POTASSIUM ION
K
NPYPAHLBTDXSSS-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
3YP PDBBind:  1ZZ3 IC50: 290 (nM) from 1 assay(s)
Binding MOAD:  1ZZ3 IC50: 290 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.76 Å
  • R-Value Free: 0.191 
  • R-Value Work: 0.156 
  • R-Value Observed: 0.158 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 68.098α = 90
b = 94.486β = 104.27
c = 122.632γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
HKL-2000data reduction
HKL-2000data scaling
SOLVEphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2005-11-29
    Type: Initial release
  • Version 1.1: 2008-04-30
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Derived calculations, Source and taxonomy, Version format compliance
  • Version 1.3: 2024-03-13
    Changes: Data collection, Database references, Derived calculations, Refinement description