Sandbox Reserved 329: Difference between revisions

[[Image:SECONDARY_STRUCTURE_SUCCESSION.jpg|thumb|left|upright=2.0|alt=Secondary Structure Succession of ATP-bound TUTases. Secondary structure residues are ordered from blue to red.|Secondary structure succession of ATP-bound TUTases.]]

Terminal uridylyl transferases (TUTases) belong to a superfamily of polymerase ß nucleotidyl transferases.<ref name="primary citation">PMID:17785418</ref> TUTases have been isolated from ''Trypanosoma brucei'' and also ''Leishmania'' ssp, parasites that cause diseases in humans such as African Sleeping Sickness.<ref>PMID:11893335</ref> TUTases can function in RNA editing; more specifically TUTase4 catalyzes a reaction that adds a nucleotide, from a nucleotide triphosphate, to uridine monophosphate (UMP), the minimally required terminal RNA substrate.<ref name="primary citation">PMID:17785418</ref> TUTase4 is able to bind to the nucleotide triphosphates ATP, CTP, GTP or UTP, however, UTP and CTP are preferred, whereas ATP and GTP ligands have been shown to cause a significant decrease in enzymatic activity.<ref name="primary citation">PMID:17785418</ref> The preference for UTP causes TUTase4 to typically add a uracil nucleotide to the RNA substrate. This selectivity has a variety of mechanisms, including a loss of coplanarity (pi-electron stacking) between the ATP and a tyrosine of the active site (Y189) required for catalysis, and reduced stacking between the UMP and ATP rings.<ref name="primary citation">PMID:17785418</ref> The RNA substrate in trypanosomal TUTases selects for cognate nucleosides and provides a metal ion binding site for Mg²⁺ ions required by the ligand.<ref name="primary citation">PMID:17785418</ref>

The uridylyl transferase bound [[ligand]] is an <scene name='Reserved_Sandbox_329/Ligand/4'>ATP complex</scene> with two Mg²⁺ ions, however many TUTases involved in RNA editing are shown to exhibit preference for binding to UTP instead.<ref name="primary citation">PMID:17785418</ref> Three <scene name='Reserved_Sandbox_329/Asp/1'>aspartate residues</scene> are conserved in TUTases, and are required for coordinating the Mg²⁺ ions in some TUTases. <ref name="primary citation">PMID:17785418</ref> Thus, these <scene name='Reserved_Sandbox_329/Asp/1'>aspartate residues</scene> are vital in catalyzing this reaction. <scene name='Sandbox_Reserved_329/Tyr189/1'>tyrosine residue</scene>