View source for 4l0f


==Structure of P450sky (CYP163B3), a cytochrome P450 from skyllamycin biosynthesis (open active site)==
<StructureSection load='4l0f' size='340' side='right'caption='[[4l0f]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4l0f]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptomyces_sp._Acta_2897 Streptomyces sp. Acta 2897]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4L0F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4L0F 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]] 1.9&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</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=4l0f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4l0f OCA], [https://pdbe.org/4l0f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4l0f RCSB], [https://www.ebi.ac.uk/pdbsum/4l0f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4l0f ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/F2YRY7_9ACTN F2YRY7_9ACTN] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The generation of modified amino acid precursors for incorporation in nonribosomal peptide synthesis (NRPS) plays a crucial, if often understated, role in the generation of peptide natural products. The biosynthesis of the cyclic depsipeptide skyllamycin requires three beta-hydroxylated amino acid precursors, with in vivo gene inactivation experiments implicating cytochrome P450sky (CYP163B3) in the hydroxylation of these amino acids. Here, we demonstrate the in vitro oxidation of l-amino acid substrates bound to peptidyl carrier protein (PCP) domains 5, 7, and 11 of the skyllamycin nonribosomal synthetase by P450sky. Selectivity for these domains over other PCP domains could be demonstrated, with hydroxylation selective for l-amino acids and stereospecific in nature resulting in the (2S,3S)-configuration. The oxidation of amino acids or small molecule substrate analogues was not supported, demonstrating the necessity of the carrier protein in P450sky-catalyzed hydroxylation. The binding of aminoacyl-PCP substrates to P450sky was detected for the catalytically active PCP7 but not for the catalytically inactive PCP10, indicating carrier protein-mediated selectivity in P450sky substrate binding. X-ray crystal structures of P450sky reveal a 3D-structure with a highly open active site, the size of which is dictated by the carrier protein bound nature of the substrate. P450sky is the first P450 demonstrated to not only interact directly with PCP-bound amino acids within the peptide-forming NRPS but also to do so with three different PCP domains in a specific fashion. This represents an expansion of the complexity and scope of NRPS-mediated peptide synthesis, with the generation of hydroxylated amino acid precursors occurring through the interaction of P450 enzymes following, rather than prior to, the selection of amino acids by NRPS-adenylation domains.

Cytochrome P450 Interacts Directly with the Nonribosomal Peptide Synthetase to Generate Three Amino Acid Precursors in Skyllamycin Biosynthesis.,Uhlmann S, Sussmuth RD, Cryle MJ ACS Chem Biol. 2013 Sep 30. PMID:24079328<ref>PMID:24079328</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4l0f" style="background-color:#fffaf0;"></div>

==See Also==
*[[Cytochrome P450 3D structures|Cytochrome P450 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: Streptomyces sp. Acta 2897]]
[[Category: Cryle MJ]]