6K4G

Crystal structure of the PI5P4Kbeta-GMPPNP complex


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.70 Å
  • R-Value Free: 0.275 
  • R-Value Work: 0.223 
  • R-Value Observed: 0.226 

Starting Model: experimental
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This is version 2.2 of the entry. See complete history

Re-refinement Note

This entry reflects an alternative modeling of the original data in: 3X04


Literature

The GTP responsiveness of PI5P4K beta evolved from a compromised trade-off between activity and specificity.

Takeuchi, K.Ikeda, Y.Senda, M.Harada, A.Okuwaki, K.Fukuzawa, K.Nakagawa, S.Yu, H.Y.Nagase, L.Imai, M.Sasaki, M.Lo, Y.H.Ito, D.Osaka, N.Fujii, Y.Sasaki, A.T.Senda, T.

(2022) Structure 

  • DOI: https://doi.org/10.1016/j.str.2022.04.004
  • Primary Citation of Related Structures:  
    6K4G, 6K4H, 7EM1, 7EM2, 7EM3, 7EM4, 7EM5, 7EM6, 7EM7, 7EM8

  • PubMed Abstract: 

    Unlike most kinases, phosphatidylinositol 5-phosphate 4-kinase β (PI5P4Kβ) utilizes GTP as a physiological phosphate donor and regulates cell growth under stress (i.e., GTP-dependent stress resilience). However, the genesis and evolution of its GTP responsiveness remain unknown. Here, we reveal that PI5P4Kβ has acquired GTP preference by generating a short dual-nucleotide-recognizing motif called the guanine efficient association (GEA) motif. Comparison of nucleobase recognition with 660 kinases and 128 G proteins has uncovered that most kinases and PI5P4Kβ use their main-chain atoms for adenine recognition, while the side-chain atoms are required for guanine recognition. Mutational analysis of the GEA motif revealed that the acquisition of GTP reactivity is accompanied by an extended activity toward inosine triphosphate (ITP) and xanthosine triphosphate (XTP). Along with the evolutionary analysis data that point to strong negative selection of the GEA motif, these results suggest that the GTP responsiveness of PI5P4Kβ has evolved from a compromised trade-off between activity and specificity, underpinning the development of the GTP-dependent stress resilience.


  • Organizational Affiliation

    Molecular Profiling Research Center for Drug Discovery and Cellular Molecular Biotechnology Research Institute, National Institute of Advanced Science and Technology, Aomi, Koto, Tokyo 135-0063, Japan; Graduate School of Pharmacological Sciences, The University of Tokyo, Hongo, Bunkyo, Tokyo 113-0033, Japan. Electronic address: [email protected].


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Phosphatidylinositol 5-phosphate 4-kinase type-2 beta
A, B
393Homo sapiensMutation(s): 0 
Gene Names: PIP4K2BPIP5K2B
EC: 2.7.1.149
UniProt & NIH Common Fund Data Resources
Find proteins for P78356 (Homo sapiens)
Explore P78356 
Go to UniProtKB:  P78356
PHAROS:  P78356
GTEx:  ENSG00000276293 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP78356
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.70 Å
  • R-Value Free: 0.275 
  • R-Value Work: 0.223 
  • R-Value Observed: 0.226 
  • Space Group: C 2 2 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 109.782α = 90
b = 184.625β = 90
c = 105.849γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
XDSdata reduction
XSCALEdata scaling
MOLREPphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
Japan Agency for Medical Research and Development (AMED)JapanJP17am0101001

Revision History  (Full details and data files)

  • Version 1.0: 2020-05-27
    Type: Initial release
  • Version 2.0: 2021-03-03
    Type: Coordinate replacement
    Reason: Real space R-factor
    Changes: Advisory, Atomic model, Data collection, Derived calculations, Other, Refinement description, Structure summary
  • Version 2.1: 2022-05-25
    Changes: Database references
  • Version 2.2: 2023-11-22
    Changes: Data collection, Refinement description