View source for 5tdc


==Crystal structure of the human UBR-box domain from UBR1 in complex with monomethylated arginine peptide.==
<StructureSection load='5tdc' size='340' side='right'caption='[[5tdc]], [[Resolution|resolution]] 1.61&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5tdc]] is a 4 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=5TDC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5TDC 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]] 1.607&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NMM:(2S)-2-AMINO-5-[(N-METHYLCARBAMIMIDOYL)AMINO]PENTANOIC+ACID'>NMM</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=5tdc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tdc OCA], [https://pdbe.org/5tdc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5tdc RCSB], [https://www.ebi.ac.uk/pdbsum/5tdc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5tdc ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/UBR1_HUMAN UBR1_HUMAN] Johanson-Blizzard syndrome. The disease is caused by mutations affecting the gene represented in this entry.
== Function ==
[https://www.uniprot.org/uniprot/UBR1_HUMAN UBR1_HUMAN] E3 ubiquitin-protein ligase which is a component of the N-end rule pathway. Recognizes and binds to proteins bearing specific N-terminal residues that are destabilizing according to the N-end rule, leading to their ubiquitination and subsequent degradation. May be involved in pancreatic homeostasis. Binds leucine and is a negative regulator of the leucine-mTOR signaling pathway, thereby controlling cell growth.<ref>PMID:15548684</ref> <ref>PMID:16311597</ref> <ref>PMID:20298436</ref> <ref>PMID:20835242</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The N-end rule pathway controls the half-life of proteins based on their N-terminal residue. Positively charged type 1 N-degrons are recognized by a negatively charged pocket on the Zn finger named the UBR box. Here, we show that the UBR box is rigid, but bound water molecules in the pocket provide the structural plasticity required to bind different positively charged amino acids. Ultra-high-resolution crystal structures of arginine, histidine, and methylated arginine reveal that water molecules mediate the binding of N-degron peptides. Using a high-throughput binding assay and isothermal titration calorimetry, we demonstrate that the UBR box is able to bind methylated arginine and lysine peptides with high affinity and measure the preference for hydrophobic residues in the second position in the N-degron peptide. Finally, we show that the V122L mutation present in Johanson-Blizzard syndrome patients changes the specificity for the second position due to occlusion of the secondary pocket.

Bound Waters Mediate Binding of Diverse Substrates to a Ubiquitin Ligase.,Munoz-Escobar J, Matta-Camacho E, Cho C, Kozlov G, Gehring K Structure. 2017 Mar 27. pii: S0969-2126(17)30064-3. doi:, 10.1016/j.str.2017.03.004. PMID:28392261<ref>PMID:28392261</ref>

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

==See Also==
*[[Ubiquitin protein ligase 3D structures|Ubiquitin protein ligase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Gehring K]]
[[Category: Kozlov G]]
[[Category: Matta-Camacho E]]
[[Category: Munoz-Escobar J]]