3re4 | pdb_00003re4

Crystal Structure of Archaeoglobus Fulgidus Rio1 Kinase bound to Toyocamycin.

spinqualitylabelsall models 3re4, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3re4 is a 2 chain structure with sequence from Arcfl. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: TO1 Related: 1zp9, 1ztf, 1zth Gene: rio1, AF_1804 (ARCFL) Activity: Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [RIO1_ARCFU] Autophosphorylation of the rio1 protein is not necessary for maintenance of kinase activity. Prefers ATP over GTP. The yeast ortholog is involved in ribosome biogenesis. Publication Abstract from PubMed 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 A 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. Interaction of rio1 kinase with toyocamycin reveals a conformational switch that controls oligomeric state and catalytic activity.,Kiburu IN, Laronde-Leblanc N PLoS One. 2012;7(5):e37371. Epub 2012 May 22. PMID:22629386 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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