View source for 5i49


==RNA Editing TUTase 1 from Trypanosoma brucei in complex with UTP analog UMPNPP==
<StructureSection load='5i49' size='340' side='right'caption='[[5i49]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5i49]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Trypanosoma_brucei Trypanosoma brucei]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5I49 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5I49 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2KH:5-O-[(S)-HYDROXY{[(S)-HYDROXY(PHOSPHONOOXY)PHOSPHORYL]AMINO}PHOSPHORYL]URIDINE'>2KH</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5i49 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5i49 OCA], [https://pdbe.org/5i49 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5i49 RCSB], [https://www.ebi.ac.uk/pdbsum/5i49 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5i49 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/TUT1_TRYBB TUT1_TRYBB] Terminal uridylyltransferase which is involved in the post-transcriptional editing of mitochondrial RNA, a process involving the addition and deletion of uridine (U) nucleotides in the pre-RNA (PubMed:11893335, PubMed:20086102, PubMed:26833087, PubMed:27744351). Specifically, catalyzes the addition of Us to the 3'-hydroxyl group of guided RNA (gRNA), ribosomal RNA (rRNA) and some mRNAs (PubMed:11893335, PubMed:20086102, PubMed:26833087, PubMed:27744351). As part of the mitochondrial 3' processome (MPsome), catalyzes the primary 3' uridylation of gRNA precursors to facilitate their recognition and to induce their processive 3'-5' degradation by DSS1, and the secondary 3' uridylation of mature gRNAs (PubMed:26833087). Involved in the 3' uridylylation of the long A/U tail of some edited and never-edited mRNAs (PubMed:20086102). Promotes 3' uridylylation-mediated decay of some never-edited mRNAs (PubMed:20086102). Does not mediate RNA-independent UTP polymerization (PubMed:27744351).<ref>PMID:11893335</ref> <ref>PMID:20086102</ref> <ref>PMID:26833087</ref> <ref>PMID:27744351</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Terminal uridyltransferases (TUTases) execute 3' RNA uridylation across protists, fungi, metazoan and plant species. Uridylation plays a particularly prominent role in RNA processing pathways of kinetoplastid protists typified by the causative agent of African sleeping sickness, Trypanosoma brucei In mitochondria of this pathogen, most mRNAs are internally modified by U-insertion/deletion editing while guide RNAs and rRNAs are U-tailed. The founding member of TUTase family, RNA editing TUTase 1 (RET1), functions as a subunit of the 3' processome in uridylation of gRNA precursors and mature guide RNAs. Along with KPAP1 poly(A) polymerase, RET1 also participates in mRNA translational activation. RET1 is divergent from human TUTases and is essential for parasite viability in the mammalian host and the insect vector. Given its robust in vitro activity, RET1 represents an attractive target for trypanocide development. Here, we report high-resolution crystal structures of the RET1 catalytic core alone and in complex with UTP analogs. These structures reveal a tight docking of the conserved nucleotidyl transferase bi-domain module with a RET1-specific C2H2 zinc finger and RNA recognition (RRM) domains. Furthermore, we define RET1 region required for incorporation into the 3' processome, determinants for RNA binding, subunit oligomerization and processive UTP incorporation, and predict druggable pockets.

RNA Editing TUTase 1: structural foundation of substrate recognition, complex interactions and drug targeting.,Rajappa-Titu L, Suematsu T, Munoz-Tello P, Long M, Demir O, Cheng KJ, Stagno JR, Luecke H, Amaro RE, Aphasizheva I, Aphasizhev R, Thore S Nucleic Acids Res. 2016 Oct 15. pii: gkw917. PMID:27744351<ref>PMID:27744351</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5i49" style="background-color:#fffaf0;"></div>

==See Also==
*[[RNA uridylyltransferase|RNA uridylyltransferase]]
== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: Trypanosoma brucei]]
[[Category: Rajappa LT]]
[[Category: Thore S]]