9hth: Difference between revisions

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'''Unreleased structure'''


The entry 9hth is ON HOLD
==Crystal structure of the fused, cysteine-less Aes123 PolB1 split intein (with S1A, N159A mutations)==
<StructureSection load='9hth' size='340' side='right'caption='[[9hth]], [[Resolution|resolution]] 1.38&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9hth]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Aeromonas_phage_Aes123 Aeromonas phage Aes123]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9HTH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9HTH 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]] 1.378&#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=9hth FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9hth OCA], [https://pdbe.org/9hth PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9hth RCSB], [https://www.ebi.ac.uk/pdbsum/9hth PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9hth ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/I6YMS9_9CAUD I6YMS9_9CAUD]
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Split inteins catalyze protein trans-splicing by ligating their extein sequences while undergoing self-excision, enabling diverse protein modification applications. However, many purified split intein precursors exhibit partial or no splicing activity for unknown reasons. The Aes123 PolB1 intein, a representative of the rare cysteine-less split inteins, is of particular interest due to its resistance to oxidative conditions and orthogonality to thiol chemistries. In this work, we identify beta-sheet-dominated aggregation of its N-terminal intein fragment as the origin of its low (~30%) splicing efficiency. Using computational, biochemical, and biophysical analyses, we characterize the fully active monomeric fraction and pinpoint aggregation-prone regions. Supported by a crystal structure, we design stably monomeric mutants with nearly complete splicing activity. The optimized CLm intein (Cysteine-Less and monomeric) retains the wild-type's ultra-fast reaction rate and serves as an efficient, thiol-independent protein modification tool. We find that other benchmark split inteins show similar precursor aggregation, suggesting that this general phenomenon arises from the intrinsic challenge to maintain the precursor in a partially disordered state while promoting stable folding upon fragment association.


Authors:  
A cysteine-less and ultra-fast split intein rationally engineered from being aggregation-prone to highly efficient in protein trans-splicing.,Humberg C, Yilmaz Z, Fitzian K, Dorner W, Kummel D, Mootz HD Nat Commun. 2025 Mar 19;16(1):2723. doi: 10.1038/s41467-025-57596-x. PMID:40108172<ref>PMID:40108172</ref>


Description:  
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[Category: Unreleased Structures]]
</div>
<div class="pdbe-citations 9hth" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Aeromonas phage Aes123]]
[[Category: Large Structures]]
[[Category: Fitzian K]]
[[Category: Humberg C]]
[[Category: Kuemmel D]]
[[Category: Mootz HD]]
[[Category: Yilmaz Z]]