Ricin: Difference between revisions
Ann Taylor (talk | contribs) No edit summary |
Ann Taylor (talk | contribs) No edit summary |
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The proposed mechanism of depurination utilizes the <scene name='Sandbox_BCMB402_Ricin/Conserved_residues/2'>conserved residues</scene> in the A chain. The aromatic ring structures of the substrate adenosine stack with the aromatic side chains of <scene name='Sandbox_BCMB402_Ricin/Tyr_stacking/1'>two tyrosine residues</scene>, Tyr 80 and 123, above and below. Hydrogen bonds form between the conserved arginine and a backbone carbonyl. The depurination reaction is aided by the protonation of N3 by Arg 180 and by ion pairing to Glu 177. A water molecule on the opposite side of the ribose is activated by hydrogen bonding to Arg 180. The activated water attacks C1' of the ribose, releasing the adenine and depurinated RNA fragment. This interferes with elongation factor binding to the ribosome, thus inhibiting [[translation|translation]]. | The proposed mechanism of depurination utilizes the <scene name='Sandbox_BCMB402_Ricin/Conserved_residues/2'>conserved residues</scene> in the A chain. The aromatic ring structures of the substrate adenosine stack with the aromatic side chains of <scene name='Sandbox_BCMB402_Ricin/Tyr_stacking/1'>two tyrosine residues</scene>, Tyr 80 and 123, above and below. Hydrogen bonds form between the conserved arginine and a backbone carbonyl. The depurination reaction is aided by the protonation of N3 by Arg 180 and by ion pairing to Glu 177. A water molecule on the opposite side of the ribose is activated by hydrogen bonding to Arg 180. The activated water attacks C1' of the ribose, releasing the adenine and depurinated RNA fragment. This interferes with elongation factor binding to the ribosome, thus inhibiting [[translation|translation]]. | ||
</StructureSection> | |||
== Site of ricin modification of rRNA == | |||
<StructureSection load='3u5d' size='400' side='right' caption='ribosomal RNA from Yeast(PDB entry [[3u5d]])' scene=''> | |||
Ricin removes an adenine from a specific portion of the 28S rRNA called the <scene name='Taylor_sandboxk_ricin_rRNA_modification_site/Sarcin-ricin_loop/1'>sacrin-ricin loop</scene>, or SRL. This <scene name='Taylor_sandboxk_ricin_rRNA_modification_site/Depurination/1'>depurination</scene> leads to reduced binding of elongation factors to the ribosome and reduced synthesis of proteins. It also triggers apoptosis via activation of the JNK pathway <ref name="Iordanov">PMID: 9154836</ref>. | |||
</StructureSection> | </StructureSection> | ||