View source for 4oqr


==Structure of a CYP105AS1 mutant in complex with compactin==
<StructureSection load='4oqr' size='340' side='right'caption='[[4oqr]], [[Resolution|resolution]] 1.81&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4oqr]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Amycolatopsis_orientalis Amycolatopsis orientalis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4OQR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4OQR 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]] 1.81&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2UO:MEVASTATIN,+COMPACTIN'>2UO</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=4oqr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4oqr OCA], [https://pdbe.org/4oqr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4oqr RCSB], [https://www.ebi.ac.uk/pdbsum/4oqr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4oqr ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/W5VH56_AMYOR W5VH56_AMYOR] Involved in the coupling of aromatic side chains of the heptapeptide of vancomycin.[ARBA:ARBA00055433]
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== Publication Abstract from PubMed ==
The cholesterol-lowering blockbuster drug pravastatin can be produced by stereoselective hydroxylation of the natural product compactin. We report here the metabolic reprogramming of the antibiotics producer Penicillium chrysogenum toward an industrial pravastatin production process. Following the successful introduction of the compactin pathway into the beta-lactam-negative P. chrysogenum DS50662, a new cytochrome P450 (P450 or CYP) from Amycolatopsis orientalis (CYP105AS1) was isolated to catalyze the final compactin hydroxylation step. Structural and biochemical characterization of the WT CYP105AS1 reveals that this CYP is an efficient compactin hydroxylase, but that predominant compactin binding modes lead mainly to the ineffective epimer 6-epi-pravastatin. To avoid costly fractionation of the epimer, the enzyme was evolved to invert stereoselectivity, producing the pharmacologically active pravastatin form. Crystal structures of the optimized mutant P450Prava bound to compactin demonstrate how the selected combination of mutations enhance compactin binding and enable positioning of the substrate for stereo-specific oxidation. Expression of P450Prava fused to a redox partner in compactin-producing P. chrysogenum yielded more than 6 g/L pravastatin at a pilot production scale, providing an effective new route to industrial scale production of an important drug.

Single-step fermentative production of the cholesterol-lowering drug pravastatin via reprogramming of Penicillium chrysogenum.,McLean KJ, Hans M, Meijrink B, van Scheppingen WB, Vollebregt A, Tee KL, van der Laan JM, Leys D, Munro AW, van den Berg MA Proc Natl Acad Sci U S A. 2015 Mar 3;112(9):2847-52. doi:, 10.1073/pnas.1419028112. Epub 2015 Feb 17. PMID:25691737<ref>PMID:25691737</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 4oqr" style="background-color:#fffaf0;"></div>

==See Also==
*[[Cytochrome P450 3D structures|Cytochrome P450 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Amycolatopsis orientalis]]
[[Category: Large Structures]]
[[Category: Leys D]]