View source for 6d31


==Structure of human Usb1 with adenosine 5'-monophosphate==
<StructureSection load='6d31' size='340' side='right'caption='[[6d31]], [[Resolution|resolution]] 1.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6d31]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6D31 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6D31 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]] 1.2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AMP:ADENOSINE+MONOPHOSPHATE'>AMP</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=6d31 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6d31 OCA], [https://pdbe.org/6d31 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6d31 RCSB], [https://www.ebi.ac.uk/pdbsum/6d31 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6d31 ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/USB1_HUMAN USB1_HUMAN] Dyskeratosis congenita;Poikiloderma with neutropenia. Poikiloderma with neutropenia (PN) [MIM:[https://omim.org/entry/604173 604173]: A genodermatosis characterized by poikiloderma, pachyonychia and chronic neutropenia. The disorder starts as a papular erythematous rash on the limbs during the first year of life. It gradually spreads centripetally and, as the papular rash resolves, hypo- and hyperpigmentation result, with development of telangiectasias. Another skin manifestation is pachyonychia, but alopecia and leukoplakia are distinctively absent. Patients have recurrent pneumonias that usually result in reactive airway disease and/or chronic cough. One of the most important extracutaneous symptoms is an increased susceptibility to infections, mainly affecting the respiratory system, primarily due to a chronic neutropenia and to neutrophil functional defects. Bone marrow abnormalities account for neutropenia and may evolve into myelodysplasia associated with the risk of leukemic transformation. Poikiloderma with neutropenia shows phenotypic overlap with Rothmund-Thomson syndrome. Note=The disease is caused by mutations affecting the gene represented in this entry.<ref>PMID:20004881</ref> <ref>PMID:20503306</ref> 
== Function ==
[https://www.uniprot.org/uniprot/USB1_HUMAN USB1_HUMAN] Phosphodiesterase responsible for the U6 snRNA 3' end processing. Acts as an exoribonuclease (RNase) responsible for trimming the poly(U) tract of the last nucleotides in the pre-U6 snRNA molecule, leading to the formation of mature U6 snRNA 3' end-terminated with a 2',3'-cyclic phosphate.<ref>PMID:22899009</ref> <ref>PMID:23190533</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Post-transcriptional modification of snRNA is central to spliceosome function. Usb1 is an exoribonuclease that shortens the oligo-uridine tail of U6 snRNA, resulting in a terminal 2',3' cyclic phosphate group in most eukaryotes, including humans. Loss of function mutations in human Usb1 cause the rare disorder poikiloderma with neutropenia (PN), and result in U6 snRNAs with elongated 3' ends that are aberrantly adenylated. Here, we show that human Usb1 removes 3' adenosines with 20-fold greater efficiency than uridines, which explains the presence of adenylated U6 snRNAs in cells lacking Usb1. We determined three high-resolution co-crystal structures of Usb1: wild-type Usb1 bound to the substrate analog adenosine 5'-monophosphate, and an inactive mutant bound to RNAs with a 3' terminal adenosine and uridine. These structures, along with QM/MM MD simulations of the catalytic mechanism, illuminate the molecular basis for preferential deadenylation of U6 snRNA. The extent of Usb1 processing is influenced by the secondary structure of U6 snRNA.

Structural and mechanistic basis for preferential deadenylation of U6 snRNA by Usb1.,Nomura Y, Roston D, Montemayor EJ, Cui Q, Butcher SE Nucleic Acids Res. 2018 Sep 12. pii: 5095463. doi: 10.1093/nar/gky812. PMID:30215753<ref>PMID:30215753</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6d31" style="background-color:#fffaf0;"></div>

==See Also==
*[[Phosphodiesterase 3D structures|Phosphodiesterase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Butcher SE]]
[[Category: Montemayor EJ]]
[[Category: Nomura Y]]