3T9E

Crystal structure of the catalytic domain of human diphosphoinositol pentakisphosphate kinase 2 (PPIP5K2) in complex with ADP, 5-(PP)-IP5 (5-IP7) and MgF3 (transition state mimic)


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.213 
  • R-Value Work: 0.173 
  • R-Value Observed: 0.175 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Structural basis for an inositol pyrophosphate kinase surmounting phosphate crowding.

Wang, H.Falck, J.R.Hall, T.M.Shears, S.B.

(2011) Nat Chem Biol 8: 111-116

  • DOI: https://doi.org/10.1038/nchembio.733
  • Primary Citation of Related Structures:  
    3T54, 3T7A, 3T99, 3T9A, 3T9B, 3T9C, 3T9D, 3T9E, 3T9F

  • PubMed Abstract: 

    Inositol pyrophosphates (such as IP7 and IP8) are multifunctional signaling molecules that regulate diverse cellular activities. Inositol pyrophosphates have 'high-energy' phosphoanhydride bonds, so their enzymatic synthesis requires that a substantial energy barrier to the transition state be overcome. Additionally, inositol pyrophosphate kinases can show stringent ligand specificity, despite the need to accommodate the steric bulk and intense electronegativity of nature's most concentrated three-dimensional array of phosphate groups. Here we examine how these catalytic challenges are met by describing the structure and reaction cycle of an inositol pyrophosphate kinase at the atomic level. We obtained crystal structures of the kinase domain of human PPIP5K2 complexed with nucleotide cofactors and either substrates, product or a MgF(3)(-) transition-state mimic. We describe the enzyme's conformational dynamics, its unprecedented topological presentation of nucleotide and inositol phosphate, and the charge balance that facilitates partly associative in-line phosphoryl transfer.


  • Organizational Affiliation

    Inositol Signaling Group, Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, USA. [email protected]


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Inositol Pyrophosphate Kinase330Homo sapiensMutation(s): 0 
Gene Names: PPIP5K2
EC: 2.7.4.24
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 4 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
I7P
Query on I7P

Download Ideal Coordinates CCD File 
C [auth A](1r,2R,3S,4s,5R,6S)-2,3,4,5,6-pentakis(phosphonooxy)cyclohexyl trihydrogen diphosphate
C6 H19 O27 P7
UPHPWXPNZIOZJL-KXXVROSKSA-N
ADP
Query on ADP

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

Download Ideal Coordinates CCD File 
I [auth A]TRIFLUOROMAGNESATE
F3 Mg
GJOMWUHGUQLOAC-UHFFFAOYSA-K
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: 0.213 
  • R-Value Work: 0.173 
  • R-Value Observed: 0.175 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 89.07α = 90
b = 109.987β = 90
c = 41.338γ = 90
Software Package:
Software NamePurpose
HKL-2000data collection
PHENIXmodel building
REFMACrefinement
HKL-2000data reduction
HKL-2000data scaling
PHENIXphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2011-12-07
    Type: Initial release
  • Version 1.1: 2011-12-14
    Changes: Database references
  • Version 1.2: 2012-01-11
    Changes: Database references
  • Version 1.3: 2024-02-28
    Changes: Data collection, Database references, Derived calculations