View source for 2wi9


==Selective oxidation of carbolide C-H bonds by engineered macrolide P450 monooxygenase==
<StructureSection load='2wi9' size='340' side='right'caption='[[2wi9]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2wi9]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptomyces_venezuelae Streptomyces venezuelae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2WI9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2WI9 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&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1D2:CYCLODODECYL+3,4,6-TRIDEOXY-3-(DIMETHYLAMINO)-BETA-D-XYLO-HEXOPYRANOSIDE'>1D2</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=2wi9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wi9 OCA], [https://pdbe.org/2wi9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2wi9 RCSB], [https://www.ebi.ac.uk/pdbsum/2wi9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2wi9 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/PIKC_STRVZ PIKC_STRVZ] Catalyzes the hydroxylation of narbomycin to give rise to pikromycin, and of 10-deoxymethymycin (YC-17) to give rise to methymycin and neomethymycin during macrolide antibiotic biosynthesis. In addition, produces low amounts of neopicromycin, novapikromycin and novamethymycin. Requires the participation of a ferredoxin and a ferredoxin reductase for the transfer of electrons from NADPH to the monooxygenase.<ref>PMID:16825192</ref> <ref>PMID:19124459</ref> <ref>PMID:19833867</ref> <ref>PMID:24627965</ref> <ref>PMID:9778370</ref> <ref>PMID:9831532</ref> 
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/wi/2wi9_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2wi9 ConSurf].
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== Publication Abstract from PubMed ==
Regio- and stereoselective oxidation of an unactivated C-H bond remains a central challenge in organic chemistry. Considerable effort has been devoted to identifying transition metal complexes, biological catalysts, or simplified mimics, but limited success has been achieved. Cytochrome P450 mono-oxygenases are involved in diverse types of regio- and stereoselective oxidations, and represent a promising biocatalyst to address this challenge. The application of this class of enzymes is particularly significant if their substrate spectra can be broadened, selectivity controlled, and reactions catalyzed in the absence of expensive heterologous redox partners. In this study, we engineered a macrolide biosynthetic P450 mono-oxygenase PikC (PikC(D50N)-RhFRED) with remarkable substrate flexibility, significantly increased activity compared to wild-type enzyme, and self-sufficiency. By harnessing its unique desosamine-anchoring functionality via a heretofore under-explored "substrate engineering" strategy, we demonstrated the ability of PikC to hydroxylate a series of carbocyclic rings linked to the desosamine glycoside via an acetal linkage (referred to as "carbolides") in a regioselective manner. Complementary analysis of a number of high-resolution enzyme-substrate cocrystal structures provided significant insights into the function of the aminosugar-derived anchoring group for control of reaction site selectivity. Moreover, unexpected biological activity of a select number of these carbolide systems revealed their potential as a previously unrecorded class of antibiotics.

Selective oxidation of carbolide C-H bonds by an engineered macrolide P450 mono-oxygenase.,Li S, Chaulagain MR, Knauff AR, Podust LM, Montgomery J, Sherman DH Proc Natl Acad Sci U S A. 2009 Oct 15. PMID:19833867<ref>PMID:19833867</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 2wi9" style="background-color:#fffaf0;"></div>

==See Also==
*[[Cytochrome P450 3D structures|Cytochrome P450 3D structures]]
*[[Cytochrome P450 hydroxylase 3D structures|Cytochrome P450 hydroxylase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Streptomyces venezuelae]]
[[Category: Chaulagain MR]]
[[Category: Knauff AR]]
[[Category: Li S]]
[[Category: Montgomery J]]
[[Category: Podust LM]]
[[Category: Sherman DH]]