View source for 3pop


==The crystal structure of GilR, an oxidoreductase that catalyzes the terminal step of gilvocarcin biosynthesis==
<StructureSection load='3pop' size='340' side='right'caption='[[3pop]], [[Resolution|resolution]] 1.65&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3pop]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptomyces_griseoflavus Streptomyces griseoflavus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3POP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3POP 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]] 1.651&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</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=3pop FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3pop OCA], [https://pdbe.org/3pop PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3pop RCSB], [https://www.ebi.ac.uk/pdbsum/3pop PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3pop ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q7X2G7_9ACTN Q7X2G7_9ACTN] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
GilR is a recently identified oxidoreductase that catalyzes the terminal step of gilvocarcin V biosynthesis and is a unique enzyme that establishes the lactone core of the polyketide-derived gilvocarcin chromophore. Gilvocarcin-type compounds form a small distinct family of anticancer agents that are involved in both photo-activated DNA-alkylation and histone H3 cross-linking. High resolution crystal structures of apoGilR and GilR in complex with its substrate pregilvocarcin V reveals that GilR belongs to the small group of a relatively new type of the vanillyl-alcohol oxidase flavoprotein family characterized by bicovalently tethered cofactors. GilR was found as a dimer, with the bicovalently attached FAD cofactor mediated through His-65 and Cys-125. Subsequent mutagenesis and functional assays indicate that Tyr-445 may be involved in reaction catalysis and in mediating the covalent attachment of FAD, whereas Tyr-448 serves as an essential residue initiating the catalysis by swinging away from the active site to accommodate binding of the 6R-configured substrate and consequently abstracting the proton of the hydroxyl residue of the substrate hemiacetal 6-OH group. These studies lay the groundwork for future enzyme engineering to broaden the substrate specificity of this bottleneck enzyme of the gilvocarcin biosynthetic pathway for the development of novel anti-cancer therapeutics.

The Crystal Structure and Mechanism of an Unusual Oxidoreductase, GilR, Involved in Gilvocarcin V Biosynthesis.,Noinaj N, Bosserman MA, Schickli MA, Piszczek G, Kharel MK, Pahari P, Buchanan SK, Rohr J J Biol Chem. 2011 Jul 1;286(26):23533-43. Epub 2011 May 10. PMID:21561854<ref>PMID:21561854</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3pop" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Streptomyces griseoflavus]]
[[Category: Bosserman MA]]
[[Category: Buchanan SK]]
[[Category: Kharel MK]]
[[Category: Noinaj N]]
[[Category: Rohr J]]
[[Category: Schickli MA]]