View source for 4cj1


==Crystal structure of CelD in complex with affitin H3==
<StructureSection load='4cj1' size='340' side='right'caption='[[4cj1]], [[Resolution|resolution]] 1.63&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4cj1]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Acetivibrio_thermocellus Acetivibrio thermocellus] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4CJ1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4CJ1 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]] 1.63&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=4cj1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cj1 OCA], [https://pdbe.org/4cj1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4cj1 RCSB], [https://www.ebi.ac.uk/pdbsum/4cj1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4cj1 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/GUND_ACETH GUND_ACETH] This enzyme catalyzes the endohydrolysis of 1,4-beta-glucosidic linkages in cellulose, lichenin and cereal beta-D-glucans.
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== Publication Abstract from PubMed ==
Glycosidases are associated with various human diseases. The development of efficient and specific inhibitors may provide powerful tools to modulate their activity. However, achieving high selectivity is a major challenge given that glycosidases with different functions can have similar enzymatic mechanisms and active-site architectures. As an alternative approach to small-chemical compounds, proteinaceous inhibitors might provide a better specificity by involving a larger surface area of interaction. We report here the design and characterization of proteinaceous inhibitors that specifically target endoglycosidases representative of the two major mechanistic classes; retaining and inverting glycosidases. These inhibitors consist of artificial affinity proteins, Affitins, selected against the thermophilic CelD from Clostridium thermocellum and lysozyme from hen egg. They were obtained from libraries of Sac7d variants, which involve either the randomization of a surface or the randomization of a surface and an artificially-extended loop. Glycosidase binders exhibited affinities in the nanomolar range with no cross-recognition, with efficient inhibition of lysozyme (Ki = 45 nM) and CelD (Ki = 95 and 111 nM), high expression yields in Escherichia coli, solubility, and thermal stabilities up to 81.1 degrees C. The crystal structures of glycosidase-Affitin complexes validate our library designs. We observed that Affitins prevented substrate access by two modes of binding; covering or penetrating the catalytic site via the extended loop. In addition, Affitins formed salt-bridges with residues essential for enzymatic activity. These results lead us to propose the use of Affitins as versatile selective glycosidase inhibitors and, potentially, as enzymatic inhibitors in general.

Potent and specific inhibition of glycosidases by small artificial binding proteins (affitins).,Correa A, Pacheco S, Mechaly AE, Obal G, Behar G, Mouratou B, Oppezzo P, Alzari PM, Pecorari F PLoS One. 2014 May 13;9(5):e97438. doi: 10.1371/journal.pone.0097438. eCollection, 2014. PMID:24823716<ref>PMID:24823716</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 4cj1" style="background-color:#fffaf0;"></div>

==See Also==
*[[Glucanase 3D structures|Glucanase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Acetivibrio thermocellus]]
[[Category: Large Structures]]
[[Category: Synthetic construct]]
[[Category: Alzari PM]]
[[Category: Behar G]]
[[Category: Correa A]]
[[Category: Mechaly AE]]
[[Category: Mouratou B]]
[[Category: Obal G]]
[[Category: Oppezzo P]]
[[Category: Pacheco S]]
[[Category: Pecorari F]]