3G5K

Structure and activity of human mitochondrial peptide deformylase, a novel cancer target


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.70 Å
  • R-Value Free: 0.193 
  • R-Value Work: 0.164 
  • R-Value Observed: 0.165 

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Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Structure and activity of human mitochondrial peptide deformylase, a novel cancer target

Escobar-Alvarez, S.Goldgur, Y.Yang, G.Ouerfelli, O.Li, Y.Scheinberg, D.A.

(2009) J Mol Biol 387: 1211-1228

  • DOI: https://doi.org/10.1016/j.jmb.2009.02.032
  • Primary Citation of Related Structures:  
    3G5K, 3G5P

  • PubMed Abstract: 

    Peptide deformylase proteins (PDFs) participate in the N-terminal methionine excision pathway of newly synthesized peptides. We show that the human PDF (HsPDF) can deformylate its putative substrates derived from mitochondrial DNA-encoded proteins. The first structural model of a mammalian PDF (1.7 A), HsPDF, shows a dimer with conserved topology of the catalytic residues and fold as non-mammalian PDFs. The HsPDF C-terminus topology and the presence of a helical loop (H2 and H3), however, shape a characteristic active site entrance. The structure of HsPDF bound to the peptidomimetic inhibitor actinonin (1.7 A) identified the substrate-binding site. A defined S1' pocket, but no S2' or S3' substrate-binding pockets, exists. A conservation of PDF-actinonin interaction across PDFs was observed. Despite the lack of true S2' and S3' binding pockets, confirmed through peptide binding modeling, enzyme kinetics suggest a combined contribution from P2'and P3' positions of a formylated peptide substrate to turnover.


  • Organizational Affiliation

    Molecular Pharmacology and Chemistry Program, Sloan-Kettering Institute, 415 E. 68th Street Zuckerman Z1941, New York, NY 10065, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Peptide deformylase, mitochondrial
A, B, C, D
183Homo sapiensMutation(s): 0 
Gene Names: PDFPDF1A
EC: 3.5.1.88
UniProt & NIH Common Fund Data Resources
Find proteins for Q9HBH1 (Homo sapiens)
Explore Q9HBH1 
Go to UniProtKB:  Q9HBH1
GTEx:  ENSG00000258429 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9HBH1
Sequence Annotations
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  • Reference Sequence
Small Molecules
Binding Affinity Annotations 
IDSourceBinding Affinity
BB2 BindingDB:  3G5K Ki: 0.3 (nM) from 1 assay(s)
IC50: min: 1.5, max: 2700 (nM) from 6 assay(s)
PDBBind:  3G5K Ki: 0.3 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.70 Å
  • R-Value Free: 0.193 
  • R-Value Work: 0.164 
  • R-Value Observed: 0.165 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 116.144α = 90
b = 77.83β = 107.46
c = 110.532γ = 90
Software Package:
Software NamePurpose
ADSCdata collection
AMoREphasing
REFMACrefinement
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: 2009-04-07
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Advisory, Refinement description, Version format compliance
  • Version 1.2: 2023-09-06
    Changes: Data collection, Database references, Derived calculations, Refinement description