View source for 5ncj


==GriE in complex with manganese, succinate and (2S,4R)-5-hydroxyleucine==
<StructureSection load='5ncj' size='340' side='right'caption='[[5ncj]], [[Resolution|resolution]] 1.53&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5ncj]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptomyces_muensis Streptomyces muensis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5NCJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5NCJ 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]] 1.529&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HL5:(2S,4R)-5-hydroxyleucine'>HL5</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=SIN:SUCCINIC+ACID'>SIN</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=5ncj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ncj OCA], [https://pdbe.org/5ncj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ncj RCSB], [https://www.ebi.ac.uk/pdbsum/5ncj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ncj ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/A0A0E3URV8_STRM4 A0A0E3URV8_STRM4] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Griselimycins (GMs) are depsidecapeptides with superb anti-tuberculosis activity. They contain up to three (2S,4R)-4-methyl-prolines (4-MePro), of which one blocks oxidative degradation and increases metabolic stability in animal models. The natural congener with this substitution is only a minor component in fermentation cultures. We showed that this product can be significantly increased by feeding the reaction with 4-MePro and we investigated the molecular basis of 4-MePro biosynthesis and incorporation. We identified the GM biosynthetic gene cluster as encoding a nonribosomal peptide synthetase and a sub-operon for 4-MePro formation. Using heterologous expression, gene inactivation, and in vitro experiments, we showed that 4-MePro is generated by leucine hydroxylation, oxidation to an aldehyde, and ring closure with subsequent reduction. The crystal structures of the leucine hydroxylase GriE have been determined in complex with substrates and products, providing insight into the stereospecificity of the reaction.

Biosynthesis of methyl-proline containing griselimycins, natural products with anti-tuberculosis activity.,Lukat P, Katsuyama Y, Wenzel S, Binz T, Konig C, Blankenfeldt W, Bronstrup M, Muller R Chem Sci. 2017 Nov 1;8(11):7521-7527. doi: 10.1039/c7sc02622f. Epub 2017 Aug 3. PMID:29163906<ref>PMID:29163906</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5ncj" style="background-color:#fffaf0;"></div>

==See Also==
*[[Hydroxylases 3D structures|Hydroxylases 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Streptomyces muensis]]
[[Category: Blankenfeldt W]]
[[Category: Lukat P]]
[[Category: Mueller R]]