View source for 8bbu


==Crystal structure of medical leech destabilase (high salt)==
<StructureSection load='8bbu' size='340' side='right'caption='[[8bbu]], [[Resolution|resolution]] 1.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8bbu]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Hirudo_medicinalis Hirudo medicinalis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8BBU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8BBU 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]] 1.1&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MLI:MALONATE+ION'>MLI</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=PCA:PYROGLUTAMIC+ACID'>PCA</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=8bbu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8bbu OCA], [https://pdbe.org/8bbu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8bbu RCSB], [https://www.ebi.ac.uk/pdbsum/8bbu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8bbu ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q25091_HIRME Q25091_HIRME] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Destabilase from the medical leech Hirudo medicinalis belongs to the family of i-type lysozymes. It has two different enzymatic activities: microbial cell walls destruction (muramidase activity), and dissolution of the stabilized fibrin (isopeptidase activity). Both activities are known to be inhibited by sodium chloride at near physiological concentrations, but the structural basis remains unknown. Here we present two crystal structures of destabilase, including a 1.1 A-resolution structure in complex with sodium ion. Our structures reveal the location of sodium ion between Glu34/Asp46 residues, which were previously recognized as a glycosidase active site. While sodium coordination with these amino acids may explain inhibition of the muramidase activity, its influence on previously suggested Ser49/Lys58 isopeptidase activity dyad is unclear. We revise the Ser49/Lys58 hypothesis and compare sequences of i-type lysozymes with confirmed destabilase activity. We suggest that the general base for the isopeptidase activity is His112 rather than Lys58. pKa calculations of these amino acids, assessed through the 1 mus molecular dynamics simulation, confirm the hypothesis. Our findings highlight the ambiguity of destabilase catalytic residues identification and build foundations for further research of structure-activity relationship of isopeptidase activity as well as structure-based protein design for potential anticoagulant drug development.

Structural insights into thrombolytic activity of destabilase from medicinal leech.,Marin E, Kornilov DA, Bukhdruker SS, Aleksenko VA, Manuvera VA, Zinovev EV, Kovalev KV, Shevtsov MB, Talyzina AA, Bobrovsky PA, Kuzmichev PK, Mishin AV, Gushchin IY, Lazarev VN, Borshchevskiy VI Sci Rep. 2023 Apr 24;13(1):6641. doi: 10.1038/s41598-023-32459-x. PMID:37095116<ref>PMID:37095116</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8bbu" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Hirudo medicinalis]]
[[Category: Large Structures]]
[[Category: Bobrovsky P]]
[[Category: Borshchevskiy V]]
[[Category: Bukhdruker S]]
[[Category: Kornilov D]]
[[Category: Lazarev V]]
[[Category: Manuvera V]]
[[Category: Marin E]]
[[Category: Zinovev E]]