3G2F

Crystal structure of the kinase domain of bone morphogenetic protein receptor type II (BMPR2) at 2.35 A resolution


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.35 Å
  • R-Value Free: 0.246 
  • R-Value Work: 0.208 
  • R-Value Observed: 0.210 

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Ligand Structure Quality Assessment 


This is version 1.5 of the entry. See complete history


Literature

Structural consequences of BMPR2 kinase domain mutations causing pulmonary arterial hypertension.

Chaikuad, A.Thangaratnarajah, C.von Delft, F.Bullock, A.N.

(2019) Sci Rep 9: 18351-18351

  • DOI: https://doi.org/10.1038/s41598-019-54830-7
  • Primary Citation of Related Structures:  
    3G2F

  • PubMed Abstract: 

    Bone morphogenetic proteins (BMPs) are secreted ligands of the transforming growth factor-β (TGF-β) family that control embryonic patterning, as well as tissue development and homeostasis. Loss of function mutations in the type II BMP receptor BMPR2 are the leading cause of pulmonary arterial hypertension (PAH), a rare disease of vascular occlusion that leads to high blood pressure in the pulmonary arteries. To understand the structural consequences of these mutations, we determined the crystal structure of the human wild-type BMPR2 kinase domain at 2.35 Å resolution. The structure revealed an active conformation of the catalytic domain that formed canonical interactions with the bound ligand Mg-ADP. Disease-associated missense mutations were mapped throughout the protein structure, but clustered predominantly in the larger kinase C-lobe. Modelling revealed that the mutations will destabilize the protein structure by varying extents consistent with their previously reported functional heterogeneity. The most severe mutations introduced steric clashes in the hydrophobic protein core, whereas those found on the protein surface were less destabilizing and potentially most favorable for therapeutic rescue strategies currently under clinical investigation.


  • Organizational Affiliation

    Structural Genomics Consortium, University of Oxford, Roosevelt Drive, Oxford, OX3 7DQ, UK.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Bone morphogenetic protein receptor type-2
A, B
336Homo sapiensMutation(s): 0 
Gene Names: BMPR2PPH1
EC: 2.7.11.30
UniProt & NIH Common Fund Data Resources
Find proteins for Q13873 (Homo sapiens)
Explore Q13873 
Go to UniProtKB:  Q13873
PHAROS:  Q13873
GTEx:  ENSG00000204217 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ13873
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 4 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
ADP
Query on ADP

Download Ideal Coordinates CCD File 
C [auth A],
I [auth B]
ADENOSINE-5'-DIPHOSPHATE
C10 H15 N5 O10 P2
XTWYTFMLZFPYCI-KQYNXXCUSA-N
SO4
Query on SO4

Download Ideal Coordinates CCD File 
E [auth A],
K [auth B]
SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
EDO
Query on EDO

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

Download Ideal Coordinates CCD File 
D [auth A],
J [auth B]
MAGNESIUM ION
Mg
JLVVSXFLKOJNIY-UHFFFAOYSA-N
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
CAS
Query on CAS
A, B
L-PEPTIDE LINKINGC5 H12 As N O2 SCYS
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.35 Å
  • R-Value Free: 0.246 
  • R-Value Work: 0.208 
  • R-Value Observed: 0.210 
  • Space Group: P 21 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 94.54α = 90
b = 218.793β = 90
c = 44.187γ = 90
Software Package:
Software NamePurpose
PHASERphasing
REFMACrefinement
MOSFLMdata reduction
SCALAdata scaling

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2009-02-17
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Advisory, Version format compliance
  • Version 1.2: 2018-01-31
    Changes: Structure summary
  • Version 1.3: 2019-04-17
    Changes: Data collection, Derived calculations, Experimental preparation
  • Version 1.4: 2019-12-18
    Changes: Database references
  • Version 1.5: 2023-09-06
    Changes: Data collection, Database references, Derived calculations, Refinement description