3pid: Difference between revisions
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< | ==The apo-form UDP-glucose 6-dehydrogenase with a C-terminal six-histidine tag== | ||
<StructureSection load='3pid' size='340' side='right'caption='[[3pid]], [[Resolution|resolution]] 1.40Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3pid]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Klebsiella_pneumoniae_subsp._pneumoniae_NTUH-K2044 Klebsiella pneumoniae subsp. pneumoniae NTUH-K2044]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3PID OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3PID 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]] 1.4Å</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=3pid FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3pid OCA], [https://pdbe.org/3pid PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3pid RCSB], [https://www.ebi.ac.uk/pdbsum/3pid PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3pid ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/A0A0J9WZA6_KLEPN A0A0J9WZA6_KLEPN] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Cationic modification of lipid A with 4-amino-4-deoxy-L-arabinopyranose (L-Ara4N) allows the pathogen Klebsiella pneumoniae to resist the antibiotic polymyxin and other cationic antimicrobial peptides. UDP-glucose dehydrogenase (Ugd) catalyzes the NAD-dependent twofold oxidation of UDP-glucose (UPG) to produce UDP-glucuronic acid (UGA), a requisite precursor in the biosynthesis of L-Ara4N and bacterial exopolysaccharides. Here we report five crystal structures of K. pneumoniae Ugd (KpUgd) in its apo form, in complex with UPG, UPG/NADH, two UGA molecules, and finally with a C-terminal His-tag. The UGA-complex structure differs from the others by a 14 degrees rotation of the N-terminal domain toward the C-terminal domain, and represents a closed enzyme conformation. It also reveals that the second UGA molecule binds to a pre-existing positively charged surface patch away from the active site. The enzyme is thus inactivated by moving the catalytically important residues C253, K256 and D257 from their original positions. Kinetic data also suggest that KpUgd has multiple binding sites for UPG, and that UGA is a competitive inhibitor. The conformational changes triggered by UGA binding to the allosteric site can be exploited in designing potent inhibitors. | |||
Conformational change upon product binding to Klebsiella pneumoniae UDP-glucose dehydrogenase: a possible inhibition mechanism for the key enzyme in polymyxin resistance.,Chen YY, Ko TP, Lin CH, Chen WH, Wang AH J Struct Biol. 2011 Sep;175(3):300-10. Epub 2011 Apr 23. PMID:21536136<ref>PMID:21536136</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 3pid" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
== | [[Category: Klebsiella pneumoniae subsp. pneumoniae NTUH-K2044]] | ||
[[Category: Large Structures]] | |||
[[Category: Chen W-H]] | |||
== | [[Category: Chen Y-Y]] | ||
< | [[Category: Ko T-P]] | ||
[[Category: Klebsiella pneumoniae]] | [[Category: Lin C-H]] | ||
[[Category: | [[Category: Wang AH-J]] | ||
[[Category: Chen | |||
[[Category: Chen | |||
[[Category: Ko | |||
[[Category: Lin | |||
[[Category: Wang | |||
Latest revision as of 20:06, 1 November 2023
The apo-form UDP-glucose 6-dehydrogenase with a C-terminal six-histidine tagThe apo-form UDP-glucose 6-dehydrogenase with a C-terminal six-histidine tag
Structural highlights
FunctionPublication Abstract from PubMedCationic modification of lipid A with 4-amino-4-deoxy-L-arabinopyranose (L-Ara4N) allows the pathogen Klebsiella pneumoniae to resist the antibiotic polymyxin and other cationic antimicrobial peptides. UDP-glucose dehydrogenase (Ugd) catalyzes the NAD-dependent twofold oxidation of UDP-glucose (UPG) to produce UDP-glucuronic acid (UGA), a requisite precursor in the biosynthesis of L-Ara4N and bacterial exopolysaccharides. Here we report five crystal structures of K. pneumoniae Ugd (KpUgd) in its apo form, in complex with UPG, UPG/NADH, two UGA molecules, and finally with a C-terminal His-tag. The UGA-complex structure differs from the others by a 14 degrees rotation of the N-terminal domain toward the C-terminal domain, and represents a closed enzyme conformation. It also reveals that the second UGA molecule binds to a pre-existing positively charged surface patch away from the active site. The enzyme is thus inactivated by moving the catalytically important residues C253, K256 and D257 from their original positions. Kinetic data also suggest that KpUgd has multiple binding sites for UPG, and that UGA is a competitive inhibitor. The conformational changes triggered by UGA binding to the allosteric site can be exploited in designing potent inhibitors. Conformational change upon product binding to Klebsiella pneumoniae UDP-glucose dehydrogenase: a possible inhibition mechanism for the key enzyme in polymyxin resistance.,Chen YY, Ko TP, Lin CH, Chen WH, Wang AH J Struct Biol. 2011 Sep;175(3):300-10. Epub 2011 Apr 23. PMID:21536136[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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