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== '''Uridylyl transferases''' ==
== '''Uridylyl transferases''' ==


[[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.]]
[[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 TUT4 with bound ATP.]]


== INTRODUCTION ==
== INTRODUCTION ==


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 Mg<sup>2+</sup> ions required by the ligand.<ref name="primary citation">PMID:17785418</ref>
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 TUT4 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 (π-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 Mg<sup>2+</sup> ions required by the ligand.<ref name="primary citation">PMID:17785418</ref>


{{STRUCTURE_2q0d | PDB=2q0d | SCENE=Reserved_Sandbox_329/Scene1/1}}
{{STRUCTURE_2q0d | PDB=2q0d | SCENE=Reserved_Sandbox_329/Scene1/1}}
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== STRUCTURE ==
== STRUCTURE ==


The uridylyl transferase bound [[ligand]] is an <scene name='Reserved_Sandbox_329/Ligand/4'>ATP complex</scene> with two Mg<sup>2+</sup> 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 Mg<sup>2+</sup> 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>
TUT4 with bound ATP <scene name='Reserved_Sandbox_329/Ligand/4'>ATP complex</scene> with two Mg<sup>2+</sup> 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 Mg<sup>2+</sup> 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>
<scene name='Sandbox_Reserved_329/Hydrophobic_hbond_interactions/1'>interactions</scene>
<scene name='Sandbox_Reserved_329/Hydrophobic_hbond_interactions/1'>interactions</scene>


Revision as of 22:18, 2 April 2011

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Uridylyl transferases

Secondary Structure Succession of ATP-bound TUTases. Secondary structure residues are ordered from blue to red.
Secondary structure succession of TUT4 with bound ATP.

INTRODUCTION

Terminal uridylyl transferases (TUTases) belong to a superfamily of polymerase ß nucleotidyl transferases.[1] TUTases have been isolated from Trypanosoma brucei and also Leishmania ssp, parasites that cause diseases in humans such as African Sleeping Sickness.[2] TUTases can function in RNA editing; more specifically TUT4 catalyzes a reaction that adds a nucleotide, from a nucleotide triphosphate, to uridine monophosphate (UMP), the minimally required terminal RNA substrate.[1] 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.[1] 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 (π-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.[1] The RNA substrate in trypanosomal TUTases selects for cognate nucleosides and provides a metal ion binding site for Mg2+ ions required by the ligand.[1]


Drag the structure with the mouse to rotate
2q0d, resolution 2.00Å (default scene)
Ligands: ATP, MG
Gene: TUT4 (Trypanosoma brucei)
Activity: RNA uridylyltransferase, with EC number 2.7.7.52
Related: 2ikf, 2nom
Resources: FirstGlance, OCA, RCSB, PDBsum
Coordinates: save as pdb, mmCIF, xml



STRUCTURE

TUT4 with bound ATP ATP complex with two Mg2+ ions, however many TUTases involved in RNA editing are shown to exhibit preference for binding to UTP instead.[1] Three aspartate residues are conserved in TUTases, and are required for coordinating the Mg2+ ions in some TUTases. [1] Thus, these aspartate residues are vital in catalyzing this reaction. tyrosine residue interactions

REFERENCES

  1. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 Stagno J, Aphasizheva I, Aphasizhev R, Luecke H. Dual role of the RNA substrate in selectivity and catalysis by terminal uridylyl transferases. Proc Natl Acad Sci U S A. 2007 Sep 11;104(37):14634-9. Epub 2007 Sep 4. PMID:17785418
  2. ↑ Aphasizhev R, Sbicego S, Peris M, Jang SH, Aphasizheva I, Simpson AM, Rivlin A, Simpson L. Trypanosome mitochondrial 3' terminal uridylyl transferase (TUTase): the key enzyme in U-insertion/deletion RNA editing. Cell. 2002 Mar 8;108(5):637-48. PMID:11893335

External Links

RCSB Protein Data Bank

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