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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 | + | [[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 | + | 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 == | ||
| - | + | 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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Contents |
Uridylyl transferases
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]
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| 2q0d, resolution 2.00Å () | |||||||||
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| Ligands: | , | ||||||||
| Gene: | TUT4 (Trypanosoma brucei) | ||||||||
| Activity: | RNA uridylyltransferase, with EC number 2.7.7.52 | ||||||||
| Related: | 2ikf, 2nom | ||||||||
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| Resources: | FirstGlance, OCA, RCSB, PDBsum | ||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||
STRUCTURE
TUT4 with bound ATP with two Mg2+ ions, however many TUTases involved in RNA editing are shown to exhibit preference for binding to UTP instead.[1] Three are conserved in TUTases, and are required for coordinating the Mg2+ ions in some TUTases. [1] Thus, these are vital in catalyzing this reaction.
REFERENCES
- ↑ 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
- ↑ 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
