View source for 4izk


==Crystal structure of yellowtail ascites virus VP4 protease active site mutant (K674A) reveals both an acyl-enzyme complex and an empty active site==
<StructureSection load='4izk' size='340' side='right'caption='[[4izk]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4izk]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Yellowtail_ascites_virus_-_Y-6 Yellowtail ascites virus - Y-6]. This structure supersedes the now removed PDB entries [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=4hhc 4hhc] and [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=3rbp 3rbp]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IZK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4IZK 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]] 2.3&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BME:BETA-MERCAPTOETHANOL'>BME</scene>, <scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=4izk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4izk OCA], [https://pdbe.org/4izk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4izk RCSB], [https://www.ebi.ac.uk/pdbsum/4izk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4izk ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/P89521_9VIRU P89521_9VIRU] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Yellowtail ascites virus (YAV) is an Aquabirnavirus that causes ascites in yellowtail, a fish often used in sushi. Segment A of the YAV genome codes for a polyprotein (pVP2-VP4-VP3) where processing by its own VP4 protease yields the capsid protein precursor pVP2, the ribonucleoprotein-forming VP3 and free VP4. VP4 protease utilizes the rarely observed serine-lysine catalytic dyad mechanism. Here we have confirmed the existence of an internal cleavage site, preceding the VP4/VP3 cleavage site. The resulting C-terminally truncated enzyme (ending at Ala716) is active as shown by a trans full-length VP4 cleavage assay and a fluorometric peptide cleavage assay. We present a crystal structure of a native active site YAV VP4 with the internal cleavage site trapped as trans product complexes and trans acyl-enzyme complexes. The acyl-enzyme complexes confirm directly the role of Ser633 as the nucleophile. A crystal structure of the lysine general base mutant (K674A) reveals the acyl-enzyme and empty binding site states of VP4, which allows for the observation of structural changes upon substrate or product binding. These snapshots of three different stages in the VP4 protease reaction mechanism will aid in the design of anti-birnavirus compounds, provide insight into previous site-directed mutagenesis results and contribute to the understanding of the serine-lysine dyad protease mechanism. In addition, we have discovered that this protease contains a channel that leads from the enzyme surface (adjacent to the substrate binding groove) to the active site and the deacylating water.

Crystal structures of Yellowtail ascites virus VP4 protease: trapping an internal cleavage site trans acyl-enzyme complex in a native Ser/Lys dyad active site.,Chung IY, Paetzel M J Biol Chem. 2013 Mar 19. PMID:23511637<ref>PMID:23511637</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4izk" style="background-color:#fffaf0;"></div>

==See Also==
*[[Rabphilin|Rabphilin]]
*[[Virus protease 3D structures|Virus protease 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: Yellowtail ascites virus - Y-6]]
[[Category: Chung IYW]]
[[Category: Paetzel M]]