1DMT

STRUCTURE OF HUMAN NEUTRAL ENDOPEPTIDASE COMPLEXED WITH PHOSPHORAMIDON

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Free: 0.242 
  • R-Value Work: 0.195 
  • R-Value Observed: 0.195 

wwPDB Validation   3D Report Full Report


This is version 1.6 of the entry. See complete history. 


Literature

Structure of human neutral endopeptidase (Neprilysin) complexed with phosphoramidon.

Oefner, C., D'Arcy, A., Hennig, M., Winkler, F.K., Dale, G.E.

(2000) J Mol Biol 296: 341-349

  • DOI: https://doi.org/10.1006/jmbi.1999.3492
  • Primary Citation of Related Structures:  
    1DMT

  • PubMed Abstract: 

    Neutral endopeptidase is a mammalian type II integral membrane zinc-containing endopeptidase, which degrades and inactivates a number of bioactive peptides. The range of substrates cleaved by neutral endopeptidase in vitro includes the enkephalins, substance P, endothelin, bradykinin and atrial natriuretic factor. Due to the physiological importance of neutral endopeptidase in the modulation of nociceptive and pressor responses there is considerable interest in inhibitors of this enzyme as novel analgesics and anti-hypertensive agents. Here we describe the crystal structure of the extracellular domain (residues 52-749) of human NEP complexed with the generic metalloproteinase inhibitor phosphoramidon at 2.1 A resolution. The structure reveals two multiply connected folding domains which embrace a large central cavity containing the active site. The inhibitor is bound to one side of this cavity and its binding mode provides a detailed understanding of the ligand-binding and specificity determinants.

    • Organizational Affiliation: 

    Pharma Preclinical Research, F. Hoffmann-La Roche Ltd., Basel, CH-4070, Switzerland.


Macromolecules
Find similar proteins by: 
(by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
NEUTRAL ENDOPEPTIDASE696Homo 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
Glycosylation
Glycosylation Sites: 3
Go to GlyGen: P08473-1
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Binding Affinity Annotations 
IDSourceBinding Affinity
RDF BindingDB:  1DMT Ki: 4 (nM) from 1 assay(s)
IC50: min: 0.4, max: 200 (nM) from 13 assay(s)
PDBBind:  1DMT IC50: 2 (nM) from 1 assay(s)
Biologically Interesting Molecules (External Reference) 1 Unique
Entity ID: 4
IDChains NameType/Class2D Diagram3D Interactions
PRD_000638 (RDF)
Query on PRD_000638		F [auth A]PHOSPHORAMIDONGlycopeptide / Enzyme inhibitor
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Free: 0.242 
  • R-Value Work: 0.195 
  • R-Value Observed: 0.195 
  • Space Group: P 32 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 107.58α = 90
b = 107.58β = 90
c = 112.84γ = 120
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
SHARPphasing
CNSrefinement

Structure Validation

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View more in-depth experimental data
Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2000-12-20
    Type: Initial release
  • Version 1.1: 2008-04-27
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Non-polymer description, Version format compliance
  • Version 1.3: 2012-12-12
    Changes: Other
  • Version 1.4: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Data collection, Derived calculations, Structure summary
  • Version 1.5: 2024-03-13
    Changes: Data collection, Database references, Source and taxonomy, Structure summary
  • Version 1.6: 2024-11-13
    Changes: Structure summary