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==DAIP in complex with a C-terminal fragment of thermolysin==
<StructureSection load='6fhp' size='340' side='right'caption='[[6fhp]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6fhp]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Geobacillus_stearothermophilus Geobacillus stearothermophilus] and [https://en.wikipedia.org/wiki/Streptomyces_mobaraensis Streptomyces mobaraensis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6FHP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6FHP 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]] 1.703&#8491;</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=6fhp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fhp OCA], [https://pdbe.org/6fhp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6fhp RCSB], [https://www.ebi.ac.uk/pdbsum/6fhp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6fhp ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/DAIP_STRMB DAIP_STRMB] Induces autolysis of dispase and thermolysin.<ref>PMID:19420706</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The Dispase autolysis-inducing protein (DAIP) is produced by Streptomyces mobaraensis to disarm neutral metalloproteases by decomposition. Absence of a catalytic protease domain led to the assumption that the seven-bladed beta-propeller protein DAIP causes structural modifications, thereby triggering autolysis. Determination of protein complexes consisting of DAIP and thermolysin or DAIP and a non-functional E138A bacillolysin variant supported this postulation. Protein twisting was indicated by DAIP-mediated inhibition of thermolysin while bacillolysin underwent immediate autolysis under the same conditions. Interestingly, increase in SYPRO orange fluorescence allowed tracking of the fast degradation process. Similarly rapid autolysis of thermolysin mediated by DAIP was only observed upon addition of amphiphilic compounds, which probably amplify the induced structural changes. DAIP further caused degradation of FITC-labelled E138A bacillolysin by trypsin, as monitored by linear decrease in fluorescence polarization. The kinetic model, calculated from the obtained data, suggested a three-step mechanism defined by (i) fast DAIP-metalloprotease complex formation, (ii) slower DAIP-mediated protein twisting and (iii) fragmentation. These results were substantiated by crystallized DAIP attached to a C-terminal helix fragment of thermolysin. Structural superposition of the complex with thermolysin is indicative of a conformational change upon binding to DAIP. Importantly, the majority of metalloproteases, also including homologs from various pathogens, are highly conserved at the autolysis-prone peptide bonds, suggesting their susceptibility to DAIP-mediated decomposition, which may offer opportunities for pharmaceutical applications. This article is protected by copyright. All rights reserved.

Destructive twisting of neutral metalloproteases: the catalysis mechanism of the Dispase autolysis-inducing protein from Streptomyces mobaraensis DSM 40487.,Fiebig D, Storka J, Roeder M, Meyners C, Schmelz S, Blankenfeldt W, Scrima A, Kolmar H, Fuchsbauer HL FEBS J. 2018 Aug 31. doi: 10.1111/febs.14647. PMID:30171661<ref>PMID:30171661</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6fhp" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Geobacillus stearothermophilus]]
[[Category: Large Structures]]
[[Category: Streptomyces mobaraensis]]
[[Category: Blankenfeldt W]]
[[Category: Fiebig D]]
[[Category: Fuchsbauer HL]]
[[Category: Schmelz S]]
[[Category: Scrima A]]