View source for 6zgp


==Crystal structure of the quaternary ammonium Rieske monooxygenase CntA in complex with inhibitor MMV12 (MMV020670)==
<StructureSection load='6zgp' size='340' side='right'caption='[[6zgp]], [[Resolution|resolution]] 2.01&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6zgp]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Acinetobacter_baumannii Acinetobacter baumannii]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ZGP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6ZGP 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]] 2.01&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=FE:FE+(III)+ION'>FE</scene>, <scene name='pdbligand=FES:FE2/S2+(INORGANIC)+CLUSTER'>FES</scene>, <scene name='pdbligand=QKQ:~{N}-(3-imidazol-1-ylpropyl)-8-(4-methoxyphenyl)-1,6-naphthyridine-2-carboxamide'>QKQ</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=6zgp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6zgp OCA], [https://pdbe.org/6zgp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6zgp RCSB], [https://www.ebi.ac.uk/pdbsum/6zgp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6zgp ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/A0A059ZPP5_ACIBA A0A059ZPP5_ACIBA] Converts carnitine to trimethylamine and malic semialdehyde.[HAMAP-Rule:MF_02097]
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Microbial metabolism of carnitine to trimethylamine (TMA) in the gut can accelerate atherosclerosis and heart disease and these TMA-producing enzymes are therefore important drug targets. Here, we report the first structures of the carnitine oxygenase CntA, an enzyme of the Rieske oxygenase family. CntA exists in a head-to-tail a3 trimeric structure. The two functional domains (the Rieske and the catalytic mononuclear iron domains) are located &gt; 40 A apart in the same monomer but adjacent in two neighbouring monomers. Structural determination of CntA and subsequent electron paramagnetic resonance measurements uncover the molecular basis of the so-called bridging glutamate (E205) residue in inter-subunit electron transfer. The structures of the substrate-bound CntA help to define the substrate pocket. Importantly, a tyrosine residue (Y203) is essential for ligand recognition through a pi-cation interaction with the quaternary ammonium group. This interaction between an aromatic residue and quaternary amine substrates allows us to delineate a subgroup of Rieske oxygenases (group V) from the prototype ring-hydroxylating Rieske oxygenases involved in bioremediation of aromatic pollutants in the environment. Furthermore, we report the discovery of the first known CntA inhibitors and solve the structure of CntA in complex with the inhibitor, demonstrating the pivotal role of Y203 through a pi-pi stacking interaction with the inhibitor. Our study provides the structural and molecular basis for future discovery of drugs targeting this TMA-producing enzyme in human gut.

Structural basis of carnitine monooxygenase CntA substrate specificity, inhibition and inter-subunit electron transfer.,Quareshy M, Shanmugam M, Townsend E, Jameson E, Bugg TDH, Cameron AD, Chen Y J Biol Chem. 2020 Nov 6. pii: RA120.016019. doi: 10.1074/jbc.RA120.016019. PMID:33158989<ref>PMID:33158989</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6zgp" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Acinetobacter baumannii]]
[[Category: Large Structures]]
[[Category: Bugg TDH]]
[[Category: Cameron A]]
[[Category: Chen Y]]
[[Category: Quareshy M]]
[[Category: Shanmugam M]]