View source for 9vdg


==Structure of a truncated loopB mutant from the human gut flora K. grimontii Apg==
<StructureSection load='9vdg' size='340' side='right'caption='[[9vdg]], [[Resolution|resolution]] 2.67&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9vdg]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Klebsiella_grimontii Klebsiella grimontii]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9VDG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9VDG 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]] 2.67&#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=9vdg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9vdg OCA], [https://pdbe.org/9vdg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9vdg RCSB], [https://www.ebi.ac.uk/pdbsum/9vdg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9vdg ProSAT]</span></td></tr>
</table>
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== Publication Abstract from PubMed ==
The clinical efficacy of the antidiabetic drug acarbose is hampered by degradation by the acarbose-preferred glucosidase (Apg) from K. grimontii TD1. Understanding the catalytic mechanism of Apg can aid the design of next-generation hypoglycemic pharmaceuticals acarbose analogs. Here, we determine several crystal structures of Apg to identify the catalytic residues and the ligand-binding pocket of Apg. Structural analyses and computational modeling reveal D448 as the active nucleophile, contrasting with prior studies that assumed D336 to be the nucleophile. In addition to E373 proposed as the proton donor in previous reports, we find that R334 might be an alternative proton donor. Our experimental and computational analyses indicate the two-ring product acarviosine is the two-step hydrolyzed product, where the second hydrolysis is the rate-limiting step. Additionally, further investigation of the acarbose analogs acarstatins A and B that are resistant to Apg is conducted by computational analysis. Overall, our studies provide perspectives into the intricacies of Apg's catalytic mechanism, contributing to the design of next-generation hypoglycemic pharmaceuticals.

Molecular insights of acarbose metabolization catalyzed by acarbose-preferred glucosidase.,Huang J, Shen Z, Xiao X, Wang L, Zhang J, Zhou J, Gu Y Nat Commun. 2025 Aug 22;16(1):7839. doi: 10.1038/s41467-025-62855-y. PMID:40846838<ref>PMID:40846838</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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== References ==
<references/>
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</StructureSection>
[[Category: Klebsiella grimontii]]
[[Category: Large Structures]]
[[Category: Huang JY]]
[[Category: Zhou JH]]