View source for 7op6


==Bacteroides thetaiotaomicron mannosidase GH2 with beta-manno-configured cyclophellitol aziridine==
<StructureSection load='7op6' size='340' side='right'caption='[[7op6]], [[Resolution|resolution]] 2.05&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7OP6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7OP6 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]] 2.05&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BR:BROMIDE+ION'>BR</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=JIT:beta-D-manno-configured+cyclophellitol+aziridine'>JIT</scene>, <scene name='pdbligand=JIW:beta-D-manno-configured+cyclophellitol+aziridine,+reacted+form'>JIW</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=VKH:(1~{R},2~{R},3~{S},4~{R},5~{R},6~{R})-5-(hydroxymethyl)-7-azabicyclo[4.1.0]heptane-2,3,4-triol'>VKH</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=7op6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7op6 OCA], [https://pdbe.org/7op6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7op6 RCSB], [https://www.ebi.ac.uk/pdbsum/7op6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7op6 ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Exo-beta-mannosidases are a broad class of stereochemically retaining hydrolases that are essential for the breakdown of complex carbohydrate substrates found in all kingdoms of life. Yet the detection of exo-beta-mannosidases in complex biological samples remains challenging, necessitating the development of new methodologies. Cyclophellitol and its analogues selectively label the catalytic nucleophiles of retaining glycoside hydrolases, making them valuable tool compounds. Furthermore, cyclophellitol can be readily redesigned to enable the incorporation of a detection tag, generating activity-based probes (ABPs) that can be used to detect and identify specific glycosidases in complex biological samples. Towards the development of ABPs for exo-beta-mannosidases, we present a concise synthesis of beta-manno-configured cyclophellitol, cyclophellitol aziridine, and N-alkyl cyclophellitol aziridines. We show that these probes covalently label exo-beta-mannosidases from GH families 2, 5, and 164. Structural studies of the resulting complexes support a canonical mechanism-based mode of action in which the active site nucleophile attacks the pseudoanomeric centre to form a stable ester linkage, mimicking the glycosyl enzyme intermediate. Furthermore, we demonstrate activity-based protein profiling using an N-alkyl aziridine derivative by specifically labelling MANBA in mouse kidney tissue. Together, these results show that synthetic manno-configured cyclophellitol analogues hold promise for detecting exo-beta-mannosidases in biological and biomedical research.

Synthesis of broad-specificity activity-based probes for exo-beta-mannosidases.,McGregor NGS, Kuo CL, Beenakker TJM, Wong CS, Offen WA, Armstrong Z, Florea BI, Codee JDC, Overkleeft HS, Aerts JMFG, Davies GJ Org Biomol Chem. 2022 Jan 26;20(4):877-886. doi: 10.1039/d1ob02287c. PMID:35015006<ref>PMID:35015006</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7op6" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Aerts JMFG]]
[[Category: Armstrong Z]]
[[Category: Beenakker TJM]]
[[Category: Codee JDC]]
[[Category: Davies GJ]]
[[Category: Florea BI]]
[[Category: Kuo C]]
[[Category: McGregor NGS]]
[[Category: Offen WA]]
[[Category: Overkleeft HS]]
[[Category: Wong C]]