2YB9

Crystal Structure of Human Neutral Endopeptidase complexed with a heteroarylalanine diacid.

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.40 Å
  • R-Value Free: 0.243 
  • R-Value Work: 0.172 
  • R-Value Observed: 0.176 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.1 of the entry. See complete history. 


Literature

Synthesis and Evaluation of Heteroarylalanine Diacids as Potent and Selective Neutral Endopeptidase Inhibitors.

Glossop, M.S., Bazin, R.J., Dack, K.N., Fox, D.N.A., Macdonald, G.A., Mills, M., Owen, D.R., Phillips, C., Reeves, K.A., Ringer, T.J., Strang, R.S., Watson, C.A.L.

(2011) Bioorg Med Chem Lett 21: 3404

  • DOI: https://doi.org/10.1016/j.bmcl.2011.03.109
  • Primary Citation of Related Structures:  
    2YB9

  • PubMed Abstract: 

    Heteroarylalanine derivatives 4 were designed as potential inhibitors of neutral endopeptidase (NEP EC 3.4.24.11). Selectivity over other zinc metalloproteinases was explored through occupation of the S2' subsite within NEP. Structural optimisation led to the identification of 5-phenyl oxazole 4f, a potent and selective NEP inhibitor. A crystal structure of the inhibitor bound complex is reported.

    • Organizational Affiliation: 

    Pfizer Global Research and Development, Ramsgate Road, Sandwich CT13 9NJ, UK. mel.s.glossop@pfizer.com


Macromolecules
Find similar proteins by: 
(by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
NEPRILYSIN696Homo sapiensMutation(s): 0 
EC: 3.4.24.11
UniProt & NIH Common Fund Data Resources
Find proteins for P08473 (Homo sapiens)
Explore P08473 
Go to UniProtKB:  P08473
PHAROS:  P08473
GTEx:  ENSG00000196549 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP08473
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
HA0
Query on HA0
Download Ideal Coordinates CCD File 
C [auth A]HETEROARYLALANINE 5-PHENYL OXAZOLE
C24 H30 N2 O6
SFZJKCPBOHKUKC-QZTJIDSGSA-N
ZN
Query on ZN
Download Ideal Coordinates CCD File 
B [auth A]ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
HA0 Binding MOAD:  2YB9 IC50: 0.6 (nM) from 1 assay(s)
PDBBind:  2YB9 IC50: 0.6 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.40 Å
  • R-Value Free: 0.243 
  • R-Value Work: 0.172 
  • R-Value Observed: 0.176 
  • Space Group: P 32 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 107.841α = 90
b = 107.841β = 90
c = 112.794γ = 120
Software Package:
Software NamePurpose
BUSTERrefinement

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


View more in-depth experimental data
Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2011-05-25
    Type: Initial release
  • Version 1.1: 2011-11-02
    Changes: Database references, Version format compliance