2P9A

E. coli methionine aminopeptidase dimetalated with inhibitor YE6


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.60 Å
  • R-Value Free: 0.231 
  • R-Value Work: 0.206 

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Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Inhibition of Monometalated Methionine Aminopeptidase: Inhibitor Discovery and Crystallographic Analysis.

Huang, M.Xie, S.X.Ma, Z.Q.Huang, Q.Q.Nan, F.J.Ye, Q.Z.

(2007) J Med Chem 50: 5735-5742

  • DOI: https://doi.org/10.1021/jm700930k
  • Primary Citation of Related Structures:  
    2P98, 2P99, 2P9A

  • PubMed Abstract: 

    Two divalent metal ions are commonly seen in the active-site cavity of methionine aminopeptidase, and at least one of the metal ions is directly involved in catalysis. Although ample structural and functional information is available for dimetalated enzyme, methionine aminopeptidase likely functions as a monometalated enzyme under physiological conditions. Information on structure, as well as catalysis and inhibition, of the monometalated enzyme is lacking. By improving conditions of high-throughput screening, we identified a unique inhibitor with specificity toward the monometalated enzyme. Kinetic characterization indicates a mutual exclusivity in binding between the inhibitor and the second metal ion at the active site. This is confirmed by X-ray structure, and this inhibitor coordinates with the first metal ion and occupies the space normally occupied by the second metal ion. Kinetic and structural analyses of the inhibition by this and other inhibitors provide insight in designing effective inhibitors of methionine aminopeptidase.


  • Organizational Affiliation

    High Throughput Screening Laboratory, University of Kansas, Lawrence, Kansas 66045, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Methionine aminopeptidase262Escherichia coliMutation(s): 0 
Gene Names: map
EC: 3.4.11.18
UniProt
Find proteins for P0AE18 (Escherichia coli (strain K12))
Explore P0AE18 
Go to UniProtKB:  P0AE18
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP0AE18
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Binding Affinity Annotations 
IDSourceBinding Affinity
YE6 BindingDB:  2P9A IC50: min: 1160, max: 7.71e+4 (nM) from 5 assay(s)
Binding MOAD:  2P9A IC50: 6560 (nM) from 1 assay(s)
PDBBind:  2P9A IC50: 6560 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.60 Å
  • R-Value Free: 0.231 
  • R-Value Work: 0.206 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 37.986α = 90
b = 60.649β = 104.82
c = 50.486γ = 90
Software Package:
Software NamePurpose
SCALAdata scaling
MOLREPphasing
CNSrefinement
PDB_EXTRACTdata extraction
MOSFLMdata reduction

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

  • Released Date: 2007-11-20 
  • Deposition Author(s): Ye, Q.

Revision History  (Full details and data files)

  • Version 1.0: 2007-11-20
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2024-02-21
    Changes: Data collection, Database references, Derived calculations