3RE4

Crystal Structure of Archaeoglobus Fulgidus Rio1 Kinase bound to Toyocamycin.


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.260 
  • R-Value Work: 0.215 
  • R-Value Observed: 0.217 

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Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Interaction of rio1 kinase with toyocamycin reveals a conformational switch that controls oligomeric state and catalytic activity.

Kiburu, I.N.Laronde-Leblanc, N.

(2012) PLoS One 7: e37371-e37371

  • DOI: https://doi.org/10.1371/journal.pone.0037371
  • Primary Citation of Related Structures:  
    3RE4

  • PubMed Abstract: 

    Rio1 kinase is an essential ribosome-processing factor required for proper maturation of 40 S ribosomal subunit. Although its structure is known, several questions regarding its functional remain to be addressed. We report that both Archaeoglobus fulgidus and human Rio1 bind more tightly to an adenosine analog, toyocamycin, than to ATP. Toyocamycin has antibiotic, antiviral and cytotoxic properties, and is known to inhibit ribosome biogenesis, specifically the maturation of 40 S. We determined the X-ray crystal structure of toyocamycin bound to Rio1 at 2.0 Å and demonstrated that toyocamycin binds in the ATP binding pocket of the protein. Despite this, measured steady state kinetics were inconsistent with strict competitive inhibition by toyocamycin. In analyzing this interaction, we discovered that Rio1 is capable of accessing multiple distinct oligomeric states and that toyocamycin may inhibit Rio1 by stabilizing a less catalytically active oligomer. We also present evidence of substrate inhibition by high concentrations of ATP for both archaeal and human Rio1. Oligomeric state studies show both proteins access a higher order oligomeric state in the presence of ATP. The study revealed that autophosphorylation by Rio1 reduces oligomer formation and promotes monomerization, resulting in the most active species. Taken together, these results suggest the activity of Rio1 may be modulated by regulating its oligomerization properties in a conserved mechanism, identifies the first ribosome processing target of toyocamycin and presents the first small molecule inhibitor of Rio1 kinase activity.


  • Organizational Affiliation

    Department of Chemistry and Biochemistry, Center for Biomolecular Structure and Organization, University of Maryland, College Park, Maryland, United States of America.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
RIO-type serine/threonine-protein kinase Rio1
A, B
258Archaeoglobus fulgidusMutation(s): 0 
Gene Names: rio1AF_1804
EC: 2.7.11.1
UniProt
Find proteins for O28471 (Archaeoglobus fulgidus (strain ATCC 49558 / DSM 4304 / JCM 9628 / NBRC 100126 / VC-16))
Explore O28471 
Go to UniProtKB:  O28471
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupO28471
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
TO1
Query on TO1

Download Ideal Coordinates CCD File 
C [auth A],
D [auth B]
4-amino-7-(beta-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile
C12 H13 N5 O4
XOKJUSAYZUAMGJ-WOUKDFQISA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
TO1 Binding MOAD:  3RE4 Kd: 40 (nM) from 1 assay(s)
PDBBind:  3RE4 Kd: 40 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.260 
  • R-Value Work: 0.215 
  • R-Value Observed: 0.217 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 52.814α = 90
b = 72.607β = 90.17
c = 60.561γ = 90
Software Package:
Software NamePurpose
HKL-2000data collection
MOLREPphasing
PHENIXrefinement
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2012-05-09
    Type: Initial release
  • Version 1.1: 2012-06-20
    Changes: Database references
  • Version 1.2: 2024-02-21
    Changes: Data collection, Database references, Derived calculations