4Q4C

Crystal structure of the catalytic domain of human diphosphoinositol pentakisphosphate kinase 2 (PPIP5K2) in complex with ADP and synthetic 1,5-(PP)2-IP4 (1,5-IP8)


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.192 
  • R-Value Work: 0.162 
  • R-Value Observed: 0.163 

Starting Model: experimental
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This is version 1.2 of the entry. See complete history


Literature

Synthesis of Densely Phosphorylated Bis-1,5-Diphospho-myo-Inositol Tetrakisphosphate and its Enantiomer by Bidirectional P-Anhydride Formation.

Capolicchio, S.Wang, H.Thakor, D.T.Shears, S.B.Jessen, H.J.

(2014) Angew Chem Int Ed Engl 53: 9508-9511

  • DOI: https://doi.org/10.1002/anie.201404398
  • Primary Citation of Related Structures:  
    4Q4C, 4Q4D

  • PubMed Abstract: 

    The ubiquitous mammalian signaling molecule bis-diphosphoinositol tetrakisphosphate (1,5-(PP)2 -myo-InsP4 , or InsP8 ) displays the most congested three-dimensional array of phosphate groups found in nature. The high charge density, the accumulation of unstable P-anhydrides and P-esters, the lack of UV absorbance, and low levels of optical rotation constitute severe obstacles to its synthesis, characterization, and purification. Herein, we describe the first procedure for the synthesis of enantiopure 1,5-(PP)2 -myo-InsP4 and 3,5-(PP)2 -myo-InsP4 utilizing a C2 -symmetric P-amidite for desymmetrization and concomitant phosphitylation followed by a one-pot bidirectional P-anhydride-forming reaction that combines sixteen chemical transformations with high efficiency. The configuration of these materials is unambiguously shown by subsequent X-ray analyses of both enantiomers after being individually soaked into crystals of the kinase domain of human diphosphoinositol pentakisphosphate kinase 2.


  • Organizational Affiliation

    Department of Chemistry, University of Zürich (UZH), Winterthurerstrasse 190, 8057 Zürich (Switzerland).


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Inositol hexakisphosphate and diphosphoinositol-pentakisphosphate kinase 2330Homo sapiensMutation(s): 0 
Gene Names: PPIP5K2HISPPD1KIAA0433VIP2
EC: 2.7.4.21 (PDB Primary Data), 2.7.4.24 (PDB Primary Data)
UniProt & NIH Common Fund Data Resources
Find proteins for O43314 (Homo sapiens)
Explore O43314 
Go to UniProtKB:  O43314
PHAROS:  O43314
GTEx:  ENSG00000145725 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupO43314
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
I8P
Query on I8P

Download Ideal Coordinates CCD File 
C [auth A](1R,3S,4R,5S,6R)-2,4,5,6-tetrakis(phosphonooxy)cyclohexane-1,3-diyl bis[trihydrogen (diphosphate)]
C6 H20 O30 P8
HHQOOERQSFJGEP-SLWYWOEDSA-N
ADP
Query on ADP

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

Download Ideal Coordinates CCD File 
D [auth A],
E [auth A],
F [auth A],
G [auth A],
H [auth A]
MAGNESIUM ION
Mg
JLVVSXFLKOJNIY-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.192 
  • R-Value Work: 0.162 
  • R-Value Observed: 0.163 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 89.519α = 90
b = 110.224β = 90
c = 41.381γ = 90
Software Package:
Software NamePurpose
HKL-2000data collection
CCP4model building
REFMACrefinement
HKL-2000data reduction
HKL-2000data scaling
CCP4phasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2014-08-06
    Type: Initial release
  • Version 1.1: 2014-09-10
    Changes: Database references
  • Version 1.2: 2023-09-20
    Changes: Data collection, Database references, Derived calculations, Refinement description