3TFY

Naa50p amino-terminal acetyltransferase bound to substrate peptide fragment and CoA


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.75 Å
  • R-Value Free: 0.254 
  • R-Value Work: 0.190 
  • R-Value Observed: 0.194 

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This is version 1.3 of the entry. See complete history


Literature

Structure of a Ternary Naa50p (NAT5/SAN) N-terminal Acetyltransferase Complex Reveals the Molecular Basis for Substrate-specific Acetylation.

Liszczak, G.Arnesen, T.Marmorstein, R.

(2011) J Biol Chem 286: 37002-37010

  • DOI: https://doi.org/10.1074/jbc.M111.282863
  • Primary Citation of Related Structures:  
    3TFY

  • PubMed Abstract: 

    The co-translational modification of N-terminal acetylation is ubiquitous among eukaryotes and has been reported to have a wide range of biological effects. The human N-terminal acetyltransferase (NAT) Naa50p (NAT5/SAN) acetylates the α-amino group of proteins containing an N-terminal methionine residue and is essential for proper sister chromatid cohesion and chromosome condensation. The elevated activity of NATs has also been correlated with cancer, making these enzymes attractive therapeutic targets. We report the x-ray crystal structure of Naa50p bound to a native substrate peptide fragment and CoA. We found that the peptide backbone of the substrate is anchored to the protein through a series of backbone hydrogen bonds with the first methionine residue specified through multiple van der Waals contacts, together creating an α-amino methionine-specific pocket. We also employed structure-based mutagenesis; the results support the importance of the α-amino methionine-specific pocket of Naa50p and are consistent with the proposal that conserved histidine and tyrosine residues play important catalytic roles. Superposition of the ternary Naa50p complex with the peptide-bound Gcn5 histone acetyltransferase revealed that the two enzymes share a Gcn5-related N-acetyltransferase fold but differ in their respective substrate-binding grooves such that Naa50p can accommodate only an α-amino substrate and not a side chain lysine substrate that is acetylated by lysine acetyltransferase enzymes such as Gcn5. The structure of the ternary Naa50p complex also provides the first molecular scaffold for the design of NAT-specific small molecule inhibitors with possible therapeutic applications.


  • Organizational Affiliation

    The Wistar Institute, Philadelphia, Pennsylvania 19104, USA.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
N-alpha-acetyltransferase 50, NatE catalytic subunitA,
C [auth B],
E [auth C]
169Homo sapiensMutation(s): 0 
Gene Names: MAK3NAA50NAT13NAT5
EC: 2.3.1
UniProt & NIH Common Fund Data Resources
Find proteins for Q9GZZ1 (Homo sapiens)
Explore Q9GZZ1 
Go to UniProtKB:  Q9GZZ1
PHAROS:  Q9GZZ1
GTEx:  ENSG00000121579 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9GZZ1
Sequence Annotations
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  • Reference Sequence

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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
hnRNP FB [auth D],
D [auth E],
F
10Homo sapiensMutation(s): 0 
Gene Names: HNRNPF
UniProt & NIH Common Fund Data Resources
Find proteins for P52597 (Homo sapiens)
Explore P52597 
Go to UniProtKB:  P52597
PHAROS:  P52597
GTEx:  ENSG00000169813 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP52597
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.75 Å
  • R-Value Free: 0.254 
  • R-Value Work: 0.190 
  • R-Value Observed: 0.194 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 48.299α = 90
b = 104.103β = 106.29
c = 68.247γ = 90
Software Package:
Software NamePurpose
HKL-2000data collection
PHASERphasing
PHENIXrefinement
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2011-09-07
    Type: Initial release
  • Version 1.1: 2011-09-21
    Changes: Database references
  • Version 1.2: 2011-11-02
    Changes: Database references
  • Version 1.3: 2023-09-13
    Changes: Data collection, Database references, Derived calculations, Refinement description