3HII

Crystal structure of human diamine oxidase in complex with the inhibitor pentamidine


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.15 Å
  • R-Value Free: 0.221 
  • R-Value Work: 0.182 
  • R-Value Observed: 0.184 

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Ligand Structure Quality Assessment 


This is version 2.2 of the entry. See complete history


Literature

Structure and inhibition of human diamine oxidase

McGrath, A.P.Hilmer, K.M.Collyer, C.A.Shepard, E.M.Elmore, B.O.Brown, D.E.Dooley, D.M.Guss, J.M.

(2009) Biochemistry 48: 9810-9822

  • DOI: https://doi.org/10.1021/bi9014192
  • Primary Citation of Related Structures:  
    3HI7, 3HIG, 3HII

  • PubMed Abstract: 

    Humans have three functioning genes that encode copper-containing amine oxidases. The product of the AOC1 gene is a so-called diamine oxidase (hDAO), named for its substrate preference for diamines, particularly histamine. hDAO has been cloned and expressed in insect cells and the structure of the native enzyme determined by X-ray crystallography to a resolution of 1.8 A. The homodimeric structure has the archetypal amine oxidase fold. Two active sites, one in each subunit, are characterized by the presence of a copper ion and a topaquinone residue formed by the post-translational modification of a tyrosine. Although hDAO shares 37.9% sequence identity with another human copper amine oxidase, semicarbazide sensitive amine oxidase or vascular adhesion protein-1, its substrate binding pocket and entry channel are distinctly different in accord with the different substrate specificities. The structures of two inhibitor complexes of hDAO, berenil and pentamidine, have been refined to resolutions of 2.1 and 2.2 A, respectively. They bind noncovalently in the active-site channel. The inhibitor binding suggests that an aspartic acid residue, conserved in all diamine oxidases but absent from other amine oxidases, is responsible for the diamine specificity by interacting with the second amino group of preferred diamine substrates.


  • Organizational Affiliation

    School of Molecular and Microbial Biosciences, University of Sydney, Sydney, NSW 2006, Australia.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Amiloride-sensitive amine oxidase
A, B
731Homo sapiensMutation(s): 1 
Gene Names: ABP1
EC: 1.4.3.22
UniProt & NIH Common Fund Data Resources
Find proteins for P19801 (Homo sapiens)
Explore P19801 
Go to UniProtKB:  P19801
PHAROS:  P19801
GTEx:  ENSG00000002726 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP19801
Sequence Annotations
Expand
  • Reference Sequence
Oligosaccharides

Help

Entity ID: 2
MoleculeChains Length2D Diagram Glycosylation3D Interactions
beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose
C
3N-Glycosylation
Glycosylation Resources
GlyTouCan:  G15407YE
GlyCosmos:  G15407YE
GlyGen:  G15407YE
Entity ID: 3
MoleculeChains Length2D Diagram Glycosylation3D Interactions
2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose
D, E, F, G, H
2N-Glycosylation
Glycosylation Resources
GlyTouCan:  G42666HT
GlyCosmos:  G42666HT
GlyGen:  G42666HT
Small Molecules
Ligands 4 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
PNT
Query on PNT

Download Ideal Coordinates CCD File 
M [auth A],
Q [auth B]
1,5-BIS(4-AMIDINOPHENOXY)PENTANE
C19 H24 N4 O2
XDRYMKDFEDOLFX-UHFFFAOYSA-N
GOL
Query on GOL

Download Ideal Coordinates CCD File 
L [auth A]GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
CU
Query on CU

Download Ideal Coordinates CCD File 
I [auth A],
N [auth B]
COPPER (II) ION
Cu
JPVYNHNXODAKFH-UHFFFAOYSA-N
CA
Query on CA

Download Ideal Coordinates CCD File 
J [auth A],
K [auth A],
O [auth B],
P [auth B]
CALCIUM ION
Ca
BHPQYMZQTOCNFJ-UHFFFAOYSA-N
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
TPQ
Query on TPQ
A, B
L-PEPTIDE LINKINGC9 H9 N O5TYR
Binding Affinity Annotations 
IDSourceBinding Affinity
PNT BindingDB:  3HII Ki: 290 (nM) from 1 assay(s)
PDBBind:  3HII Ki: 290 (nM) from 1 assay(s)
Binding MOAD:  3HII Ki: 290 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.15 Å
  • R-Value Free: 0.221 
  • R-Value Work: 0.182 
  • R-Value Observed: 0.184 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 92.455α = 90
b = 94.69β = 90
c = 196.279γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
REFMACrefinement
PDB_EXTRACTdata extraction
Blu-Icedata collection
HKL-2000data reduction
HKL-2000data scaling
REFMACphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2009-10-20
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Derived calculations, Non-polymer description, Version format compliance
  • Version 1.2: 2017-11-01
    Changes: Refinement description
  • Version 2.0: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Atomic model, Data collection, Derived calculations, Structure summary
  • Version 2.1: 2021-11-10
    Changes: Database references, Structure summary
  • Version 2.2: 2023-11-01
    Changes: Data collection, Refinement description