3RE4

Crystal Structure of Archaeoglobus Fulgidus Rio1 Kinase bound to Toyocamycin.

Summary for 3RE4

• Entry DOI: 10.2210/pdb3re4/pdb
• Related: 1ZP9 1ZTF 1ZTH
• Descriptor: RIO-type serine/threonine-protein kinase Rio1, 4-amino-7-(beta-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile (3 entities in total)
• Functional Keywords: atypical kinase, transferase-antibiotic complex, transferase/antibiotic
• Biological source: Archaeoglobus fulgidus
• Total number of polymer chains: 2
• Total formula weight: 60857.85

Authors

Kiburu, I.N.,LaRonde-LeBlanc, N. (deposition date: 2011-04-02, release date: 2012-05-09, Last modification date: 2024-02-21)

Primary citation

Kiburu, I.N.,Laronde-Leblanc, N.
Interaction of rio1 kinase with toyocamycin reveals a conformational switch that controls oligomeric state and catalytic activity.
Plos One, 7:e37371-e37371, 2012

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.

PubMed: 22629386
DOI: 10.1371/journal.pone.0037371

Experimental method

X-RAY DIFFRACTION (1.997 Å)