3LGD

Crystal structure of human adenosine deaminase growth factor, adenosine deaminase type 2 (ADA2)


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.234 
  • R-Value Work: 0.185 
  • R-Value Observed: 0.187 

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This is version 1.2 of the entry. See complete history


Literature

Structural basis for the growth factor activity of human adenosine deaminase ADA2.

Zavialov, A.V.Yu, X.Spillmann, D.Lauvau, G.Zavialov, A.V.

(2010) J Biol Chem 285: 12367-12377

  • DOI: https://doi.org/10.1074/jbc.M109.083527
  • Primary Citation of Related Structures:  
    3LGD, 3LGG

  • PubMed Abstract: 

    Two distinct adenosine deaminases, ADA1 and ADA2, are found in humans. ADA1 has an important role in lymphocyte function and inherited mutations in ADA1 result in severe combined immunodeficiency. The recently isolated ADA2 belongs to the novel family of adenosine deaminase growth factors (ADGFs), which play an important role in tissue development. The crystal structures of ADA2 and ADA2 bound to a transition state analogue presented here reveal the structural basis of the catalytic/signaling activity of ADGF/ADA2 proteins. In addition to the catalytic domain, the structures discovered two ADGF/ADA2-specific domains of novel folds that mediate the protein dimerization and binding to the cell surface receptors. This complex architecture is in sharp contrast with that of monomeric single domain ADA1. An extensive glycosylation and the presence of a conserved disulfide bond and a signal peptide in ADA2 strongly suggest that ADA2, in contrast to ADA1, is specifically designed to act in the extracellular environment. The comparison of catalytic sites of ADA2 and ADA1 demonstrates large differences in the arrangement of the substrate-binding pockets. These structural differences explain the substrate and inhibitor specificity of adenosine deaminases and provide the basis for a rational design of ADA2-targeting drugs to modulate the immune system responses in pathophysiological conditions.


  • Organizational Affiliation

    Department of Molecular Biology, Uppsala Biomedical Centre, Swedish University of Agricultural Sciences, Uppsala, Sweden.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Adenosine deaminase CECR1
A, B
508Homo sapiensMutation(s): 0 
Gene Names: ADA2CECR1CECR1/ADA2IDGFL
EC: 3.5.4.4
UniProt & NIH Common Fund Data Resources
Find proteins for Q9NZK5 (Homo sapiens)
Explore Q9NZK5 
Go to UniProtKB:  Q9NZK5
PHAROS:  Q9NZK5
GTEx:  ENSG00000093072 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9NZK5
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 4 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
NAG
Query on NAG

Download Ideal Coordinates CCD File 
C [auth A]
D [auth A]
E [auth A]
I [auth B]
J [auth B]
C [auth A],
D [auth A],
E [auth A],
I [auth B],
J [auth B],
K [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 
F [auth A],
L [auth B]
ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
EDO
Query on EDO

Download Ideal Coordinates CCD File 
G [auth A],
M [auth B]
1,2-ETHANEDIOL
C2 H6 O2
LYCAIKOWRPUZTN-UHFFFAOYSA-N
UNX
Query on UNX

Download Ideal Coordinates CCD File 
H [auth A],
N [auth B]
UNKNOWN ATOM OR ION
X
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.234 
  • R-Value Work: 0.185 
  • R-Value Observed: 0.187 
  • Space Group: P 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 63.212α = 113.38
b = 73.099β = 94.18
c = 80.662γ = 92.16
Software Package:
Software NamePurpose
DNAdata collection
PHENIXmodel building
REFMACrefinement
MOSFLMdata reduction
SCALAdata scaling
PHENIXphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2010-02-09
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Advisory, Data collection, Database references, Derived calculations, Structure summary