4ZR5

Soluble rabbit neprilysin in complex with phosphoramidon

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.80 Å
  • R-Value Free: 0.227 
  • R-Value Work: 0.192 
  • R-Value Observed: 0.194 

Starting Model: experimental
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This is version 2.2 of the entry. See complete history. 


Literature

Structures of soluble rabbit neprilysin complexed with phosphoramidon or thiorphan.

Labiuk, S.L., Sygusch, J., Grochulski, P.

(2019) Acta Crystallogr F Struct Biol Commun 75: 405-411

  • DOI: https://doi.org/10.1107/S2053230X19006046
  • Primary Citation of Related Structures:  
    4XBH, 4ZR5, 5V48

  • PubMed Abstract: 

    Neutral endopeptidase (neprilysin; NEP) is a proteinase that cleaves a wide variety of peptides and has been implicated in Alzheimer's disease, cardiovascular conditions, arthritis and other inflammatory diseases. The structure of the soluble extracellular domain (residues 55-750) of rabbit neprilysin was solved both in its native form at 2.1 Å resolution, and bound to the inhibitors phosphoramidon and thiorphan at 2.8 and 3.0 Å resolution, respectively. Consistent with the extracellular domain of human neprilysin, the structure reveals a large central cavity which contains the active site and the location for inhibitor binding.

    • Organizational Affiliation: 

    Canadian Light Source, 44 Innovation Boulevard, Saskatoon, SK S7N 2V3, Canada.


Macromolecules
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(by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Neprilysin
A, B
696Oryctolagus cuniculusMutation(s): 0 
Gene Names: MME
EC: 3.4.24.11
UniProt
Find proteins for P08049 (Oryctolagus cuniculus)
Explore P08049 
Go to UniProtKB:  P08049
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP08049
Glycosylation
Glycosylation Sites: 3
Sequence Annotations
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  • Reference Sequence
Oligosaccharides

Help

Entity ID: 2
MoleculeChains Length2D Diagram Glycosylation3D Interactions
2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose
C, D, E, F
2N-Glycosylation
Glycosylation Resources
GlyTouCan:  G42666HT
GlyCosmos:  G42666HT
GlyGen:  G42666HT
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
RDF
Query on RDF
Download Ideal Coordinates CCD File 
H [auth A],
K [auth B]		N-ALPHA-L-RHAMNOPYRANOSYLOXY(HYDROXYPHOSPHINYL)-L-LEUCYL-L-TRYPTOPHAN
C23 H34 N3 O10 P
ZPHBZEQOLSRPAK-XLCYBJAPSA-N
NAG
Query on NAG
Download Ideal Coordinates CCD File 
I [auth A],
L [auth B]		2-acetamido-2-deoxy-beta-D-glucopyranose
C8 H15 N O6
OVRNDRQMDRJTHS-FMDGEEDCSA-N
ZN
Query on ZN
Download Ideal Coordinates CCD File 
G [auth A],
J [auth B]		ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
RDF BindingDB:  4ZR5 Ki: 4 (nM) from 1 assay(s)
IC50: min: 0.4, max: 200 (nM) from 13 assay(s)
Biologically Interesting Molecules (External Reference) 1 Unique
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.80 Å
  • R-Value Free: 0.227 
  • R-Value Work: 0.192 
  • R-Value Observed: 0.194 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 68.513α = 90
b = 107.446β = 90
c = 210.589γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
PHENIXrefinement
PDB_EXTRACTdata extraction

Structure Validation

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Entry History & Funding Information

Deposition Data

Funding OrganizationLocationGrant Number
Medical Research Council (MRC, Canada)Canada--

Revision History  (Full details and data files)

  • Version 1.0: 2016-06-08
    Type: Initial release
  • Version 1.1: 2016-10-26
    Changes: Non-polymer description
  • Version 1.2: 2017-09-06
    Changes: Author supporting evidence, Derived calculations
  • Version 1.3: 2019-06-26
    Changes: Data collection, Database references
  • Version 1.4: 2019-11-13
    Changes: Database references
  • Version 1.5: 2020-01-08
    Changes: Author supporting evidence
  • Version 2.0: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Atomic model, Data collection, Derived calculations, Structure summary
  • Version 2.1: 2023-09-27
    Changes: Data collection, Database references, Refinement description, Structure summary
  • Version 2.2: 2024-10-23
    Changes: Structure summary