2c6h

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[[Image:2c6h.png|left|200px]]
 
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==Crystal structure of YC-17-bound cytochrome P450 PikC (CYP107L1)==
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The line below this paragraph, containing "STRUCTURE_2c6h", creates the "Structure Box" on the page.
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<StructureSection load='2c6h' size='340' side='right'caption='[[2c6h]], [[Resolution|resolution]] 2.35&Aring;' scene=''>
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[2c6h]] 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=2C6H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2C6H FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.35&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=PXI:4-{[4-(DIMETHYLAMINO)-3-HYDROXY-6-METHYLTETRAHYDRO-2H-PYRAN-2-YL]OXY}-12-ETHYL-3,5,7,11-TETRAMETHYLOXACYCLODODEC-9-ENE-2,8-DIONE'>PXI</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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{{STRUCTURE_2c6h| PDB=2c6h | SCENE= }}
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2c6h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2c6h OCA], [https://pdbe.org/2c6h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2c6h RCSB], [https://www.ebi.ac.uk/pdbsum/2c6h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2c6h ProSAT]</span></td></tr>
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</table>
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== Function ==
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[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>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/c6/2c6h_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=2c6h ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The pikromycin (Pik)/methymycin biosynthetic pathway of Streptomyces venezuelae represents a valuable system for dissecting the fundamental mechanisms of modular polyketide biosynthesis, aminodeoxysugar assembly, glycosyltransfer, and hydroxylation leading to the production of a series of macrolide antibiotics, including the natural ketolides narbomycin and pikromycin. In this study, we describe four x-ray crystal structures and allied functional studies for PikC, the remarkable P450 monooxygenase responsible for production of a number of related macrolide products from the Pik pathway. The results provide important new insights into the structural basis for the C10/C12 and C12/C14 hydroxylation patterns for the 12-(YC-17) and 14-membered ring (narbomycin) macrolides, respectively. This includes two different ligand-free structures in an asymmetric unit (resolution 2.1 A) and two co-crystal structures with bound endogenous substrates YC-17 (resolution 2.35 A)or narbomycin (resolution 1.7 A). A central feature of the enzyme-substrate interaction involves anchoring of the desosamine residue in two alternative binding pockets based on a series of distinct amino acid residues that form a salt bridge and a hydrogen-bonding network with the deoxysugar C3' dimethylamino group. Functional significance of the salt bridge was corroborated by site-directed mutagenesis that revealed a key role for Glu-94 in YC-17 binding and Glu-85 for narbomycin binding. Taken together, the x-ray structure analysis, site-directed mutagenesis, and corresponding product distribution studies reveal that PikC substrate tolerance and product diversity result from a combination of alternative anchoring modes rather than an induced fit mechanism.
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===CRYSTAL STRUCTURE OF YC-17-BOUND CYTOCHROME P450 PIKC (CYP107L1)===
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The structural basis for substrate anchoring, active site selectivity, and product formation by P450 PikC from Streptomyces venezuelae.,Sherman DH, Li S, Yermalitskaya LV, Kim Y, Smith JA, Waterman MR, Podust LM J Biol Chem. 2006 Sep 8;281(36):26289-97. Epub 2006 Jul 6. PMID:16825192<ref>PMID:16825192</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 2c6h" style="background-color:#fffaf0;"></div>
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(as it appears on PubMed at http://www.pubmed.gov), where 16825192 is the PubMed ID number.
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{{ABSTRACT_PUBMED_16825192}}
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==About this Structure==
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[[2c6h]] is a 2 chain structure of [[Cytochrome P450]] with sequence from [http://en.wikipedia.org/wiki/Streptomyces_venezuelae Streptomyces venezuelae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2C6H OCA].
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==See Also==
==See Also==
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*[[Cytochrome P450]]
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*[[Cytochrome P450 3D structures|Cytochrome P450 3D structures]]
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*[[Cytochrome P450 hydroxylase 3D structures|Cytochrome P450 hydroxylase 3D structures]]
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==Reference==
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== References ==
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<ref group="xtra">PMID:16825192</ref><references group="xtra"/>
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Large Structures]]
[[Category: Streptomyces venezuelae]]
[[Category: Streptomyces venezuelae]]
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[[Category: Kim, Y.]]
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[[Category: Kim Y]]
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[[Category: Li, S.]]
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[[Category: Li S]]
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[[Category: Podust, L M.]]
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[[Category: Podust LM]]
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[[Category: Sherman, D H.]]
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[[Category: Sherman DH]]
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[[Category: Smith, J A.]]
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[[Category: Smith JA]]
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[[Category: Waterman, M R.]]
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[[Category: Waterman MR]]
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[[Category: Yermalitskaya, L V.]]
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[[Category: Yermalitskaya LV]]
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[[Category: Antibiotic biosynthesis]]
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[[Category: Cyp107l1]]
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[[Category: Cytochrome p450]]
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[[Category: Heme]]
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[[Category: Iron]]
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[[Category: Macrolide monooxygenase]]
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[[Category: Metal-binding]]
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[[Category: Monooxygenase]]
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[[Category: Oxidoreductase]]
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[[Category: Oxidoreductase antibiotic biosynthesis]]
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[[Category: Pikc]]
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Current revision

Crystal structure of YC-17-bound cytochrome P450 PikC (CYP107L1)

PDB ID 2c6h

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