9GN7

Crystal Structure of Deacetylase (HdaH) from Klebsiella pneumoniae subsp. ozaenae in Complex with the inhibitor TSA


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.18 Å
  • R-Value Free: 0.186 
  • R-Value Work: 0.148 

Starting Model: experimental
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Literature

Distribution and diversity of classical deacylases in bacteria.

Graf, L.G.Moreno-Yruela, C.Qin, C.Schulze, S.Palm, G.J.Schmoker, O.Wang, N.Hocking, D.M.Jebeli, L.Girbardt, B.Berndt, L.Dorre, B.Weis, D.M.Janetzky, M.Albrecht, D.Zuhlke, D.Sievers, S.Strugnell, R.A.Olsen, C.A.Hofmann, K.Lammers, M.

(2024) Nat Commun 15: 9496-9496

  • DOI: https://doi.org/10.1038/s41467-024-53903-0
  • Primary Citation of Related Structures:  
    9GKU, 9GKV, 9GKW, 9GKX, 9GKY, 9GKZ, 9GL0, 9GL1, 9GLB, 9GN1, 9GN6, 9GN7

  • PubMed Abstract: 

    Classical Zn 2+ -dependent deac(et)ylases play fundamental regulatory roles in life and are well characterized in eukaryotes regarding their structures, substrates and physiological roles. In bacteria, however, classical deacylases are less well understood. We construct a Generalized Profile (GP) and identify thousands of uncharacterized classical deacylases in bacteria, which are grouped into five clusters. Systematic structural and functional characterization of representative enzymes from each cluster reveal high functional diversity, including polyamine deacylases and protein deacylases with various acyl-chain type preferences. These data are supported by multiple crystal structures of enzymes from different clusters. Through this extensive analysis, we define the structural requirements of substrate selectivity, and discovered bacterial de-D-/L-lactylases and long-chain deacylases. Importantly, bacterial deacylases are inhibited by archetypal HDAC inhibitors, as supported by co-crystal structures with the inhibitors SAHA and TSA, and setting the ground for drug repurposing strategies to fight bacterial infections. Thus, we provide a systematic structure-function analysis of classical deacylases in bacteria and reveal the basis of substrate specificity, acyl-chain preference and inhibition.


  • Organizational Affiliation

    Department Synthetic and Structural Biochemistry, Institute of Biochemistry, University of Greifswald, Greifswald, Germany.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Deacetylase382Klebsiella pneumoniae subsp. ozaenaeMutation(s): 0 
Gene Names: hdaHNCTC10313_02007NCTC5050_05964
EC: 3.5.1
UniProt
Find proteins for A0A377Z5F6 (Klebsiella pneumoniae subsp. ozaenae)
Explore A0A377Z5F6 
Go to UniProtKB:  A0A377Z5F6
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupA0A377Z5F6
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 5 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
TSN (Subject of Investigation/LOI)
Query on TSN

Download Ideal Coordinates CCD File 
F [auth A]TRICHOSTATIN A
C17 H22 N2 O3
RTKIYFITIVXBLE-QEQCGCAPSA-N
PO4
Query on PO4

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E [auth A]PHOSPHATE ION
O4 P
NBIIXXVUZAFLBC-UHFFFAOYSA-K
GOL
Query on GOL

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G [auth A],
H [auth A]
GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
ZN (Subject of Investigation/LOI)
Query on ZN

Download Ideal Coordinates CCD File 
D [auth A]ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
K
Query on K

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B [auth A],
C [auth A]
POTASSIUM ION
K
NPYPAHLBTDXSSS-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.18 Å
  • R-Value Free: 0.186 
  • R-Value Work: 0.148 
  • Space Group: I 2 3
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 146.57α = 90
b = 146.57β = 90
c = 146.57γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
REFMACrefinement
XDSdata reduction
XDSdata scaling
PHASERphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
German Research Foundation (DFG)GermanyLA2984/6-1

Revision History  (Full details and data files)

  • Version 1.0: 2024-11-06
    Type: Initial release
  • Version 1.1: 2024-11-13
    Changes: Database references