View source for 5eku


==Crystal Structure of Trypanosoma Brucei Protein Arginine Methyltransferase PRMT7 in complex with S-Adenosyl-L-homocysteine==
<StructureSection load='5eku' size='340' side='right'caption='[[5eku]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5eku]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Trypanosoma_brucei_brucei Trypanosoma brucei brucei]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5EKU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5EKU 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]] 2.801&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</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=5eku FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5eku OCA], [https://pdbe.org/5eku PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5eku RCSB], [https://www.ebi.ac.uk/pdbsum/5eku PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5eku ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/D6XJ80_TRYB2 D6XJ80_TRYB2] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Trypanosoma brucei PRMT7 (TbPRMT7) is a protein arginine methyltransferase (PRMT) that strictly monomethylates various substrates, thus classifying it as a type III PRMT. However, the molecular basis of its unique product specificity has remained elusive. Here, we present the structure of TbPRMT7 in complex with its cofactor product S-adenosyl-l-homocysteine (AdoHcy) at 2.8 A resolution and identify a glutamate residue critical for its monomethylation behavior. TbPRMT7 comprises the conserved methyltransferase and beta-barrel domains, an N-terminal extension, and a dimerization arm. The active site at the interface of the N-terminal extension, methyltransferase, and beta-barrel domains is stabilized by the dimerization arm of the neighboring protomer, providing a structural basis for dimerization as a prerequisite for catalytic activity. Mutagenesis of active-site residues highlights the importance of Glu181, the second of the two invariant glutamate residues of the double E loop that coordinate the target arginine in substrate peptides/proteins and that increase its nucleophilicity. Strikingly, mutation of Glu181 to aspartate converts TbPRMT7 into a type I PRMT, producing asymmetric dimethylarginine (ADMA). Isothermal titration calorimetry (ITC) using a histone H4 peptide showed that the Glu181Asp mutant has markedly increased affinity for monomethylated peptide with respect to the WT, suggesting that the enlarged active site can favorably accommodate monomethylated peptide and provide sufficient space for ADMA formation. In conclusion, these findings yield valuable insights into the product specificity and the catalytic mechanism of protein arginine methyltransferases and have important implications for the rational (re)design of PRMTs.

A glutamate/aspartate switch controls product specificity in a protein arginine methyltransferase.,Debler EW, Jain K, Warmack RA, Feng Y, Clarke SG, Blobel G, Stavropoulos P Proc Natl Acad Sci U S A. 2016 Feb 23;113(8):2068-73. doi:, 10.1073/pnas.1525783113. Epub 2016 Feb 8. PMID:26858449<ref>PMID:26858449</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5eku" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: Trypanosoma brucei brucei]]
[[Category: Debler EW]]
[[Category: Stavropoulos P]]