View source for 6vhw


==Klebsiella oxytoca NpsA N-terminal subdomain in complex with 3-hydroxybenzoyl-AMSN==
<StructureSection load='6vhw' size='340' side='right'caption='[[6vhw]], [[Resolution|resolution]] 1.83&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6vhw]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Klebsiella_oxytoca Klebsiella oxytoca]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6VHW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6VHW 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]] 1.83&#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=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene>, <scene name='pdbligand=R2V:5-deoxy-5-{[(3-hydroxybenzene-1-carbonyl)sulfamoyl]amino}adenosine'>R2V</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=6vhw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vhw OCA], [https://pdbe.org/6vhw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6vhw RCSB], [https://www.ebi.ac.uk/pdbsum/6vhw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6vhw ProSAT]</span></td></tr>
</table>
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== Publication Abstract from PubMed ==
Tilimycin is an enterotoxin produced by the opportunistic pathogen Klebsiella oxytoca that causes antibiotic-associated hemorrhagic colitis (AAHC). This pyrrolobenzodiazepine (PBD) natural product is synthesized by a bimodular nonribosomal peptide synthetase (NRPS) pathway composed of three proteins: NpsA, ThdA, and NpsB. We describe the functional and structural characterization of the fully reconstituted NRPS system and report the steady-state kinetic analysis of all natural substrates and cofactors as well as the structural characterization of both NpsA and ThdA. The mechanism of action of tilimycin was confirmed using DNA adductomics techniques through the detection of putative N-2 guanine alkylation after tilimycin exposure to eukaryotic cells, providing the first structural characterization of a PBD-DNA adduct formed in cells. Finally, we report the rational design of small-molecule inhibitors that block tilimycin biosynthesis in whole cell K. oxytoca (IC50 = 29 +/- 4 muM) through the inhibition of NpsA (KD = 29 +/- 4 nM).

Biosynthesis, Mechanism of Action, and Inhibition of the Enterotoxin Tilimycin Produced by the Opportunistic Pathogen Klebsiella oxytoca.,Alexander EM, Kreitler DF, Guidolin V, Hurben AK, Drake E, Villalta PW, Balbo S, Gulick AM, Aldrich CC ACS Infect Dis. 2020 Jun 24. doi: 10.1021/acsinfecdis.0c00326. PMID:32485104<ref>PMID:32485104</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6vhw" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Klebsiella oxytoca]]
[[Category: Large Structures]]
[[Category: Gulick AM]]
[[Category: Kreitler DF]]