View source for 8vyy


==The crystal structure of MarE in complex with its native substrate, beta-methyl-L-tryptophan==
<StructureSection load='8vyy' size='340' side='right'caption='[[8vyy]], [[Resolution|resolution]] 2.45&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8vyy]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptomyces_sp. Streptomyces sp.]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8VYY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8VYY 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]] 2.45&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=78U:(BETAS)-BETA-METHYL-L-TRYPTOPHAN'>78U</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</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=8vyy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8vyy OCA], [https://pdbe.org/8vyy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8vyy RCSB], [https://www.ebi.ac.uk/pdbsum/8vyy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8vyy ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/X2D878_9ACTN X2D878_9ACTN] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
MarE, a heme-dependent enzyme, catalyzes a unique 2-oxindole-forming monooxygenation reaction from tryptophan metabolites. To elucidate its enzyme-substrate interaction mode, we present the first X-ray crystal structures of MarE in complex with its prime substrate, (2S,3S)-beta-methyl-l-tryptophan and cyanide at 1.89 A resolution as well as a truncated yet catalytically active version in complex with the substrate at 2.45 A resolution. These structures establish MarE as a member of the heme-dependent aromatic oxygenase (HDAO) superfamily and reveal its evolutionary link to indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO). While MarE adopts a global structure resembling the homotetrameric TDO, it features a simplified alpha6 helix compared to TDO's more elaborate alphaE and alphaH helices with additional alphaF and alphaG regions. Despite differing oxygen activation outcomes, MarE shares a substrate binding mode similar to IDO and TDO, with the indole nitrogen of its substrate oriented toward the heme iron in the ternary cyano complex, interacting with His55. The substrate's carboxylate group engages Arg118, with mutational studies confirming the roles of these residues in substrate binding. However, the second-sphere interactions with the substrate's alpha-amino nitrogen differ between MarE and TDO, and the substrate's orientation in the binary complex remains ambiguous due to two possible conformations. Notably, TDO features an extensive hydrogen-bonding network around the heme propionate below the heme plane, which is absent in MarE, suggesting mechanistic differences. These structural insights lay a foundation for further mechanistic studies, particularly for understanding how heme-dependent enzymes oxygenate tryptophan-derived metabolites.

Structural insights into 2-oxindole-forming monooxygenase MarE: Divergent architecture and substrate positioning versus tryptophan dioxygenases.,Shin I, Nguyen RC, Montoya SR, Liu A J Biol Chem. 2025 Jan 27;301(3):108241. doi: 10.1016/j.jbc.2025.108241. PMID:39880093<ref>PMID:39880093</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8vyy" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Streptomyces sp]]
[[Category: Liu A]]
[[Category: Shin I]]