2vzm

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[[Image:2vzm.png|left|200px]]
 
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==Crystal structure of the narbomycin-bound PikC D50N mutant==
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The line below this paragraph, containing "STRUCTURE_2vzm", creates the "Structure Box" on the page.
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<StructureSection load='2vzm' size='340' side='right'caption='[[2vzm]], [[Resolution|resolution]] 1.85&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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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'>[[2vzm]] 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=2VZM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2VZM FirstGlance]. <br>
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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]] 1.85&#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=NRB:NARBOMYCIN'>NRB</scene></td></tr>
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{{STRUCTURE_2vzm| PDB=2vzm | 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=2vzm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vzm OCA], [https://pdbe.org/2vzm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2vzm RCSB], [https://www.ebi.ac.uk/pdbsum/2vzm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2vzm 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/vz/2vzm_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=2vzm 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 cytochrome P-450 PikC from Streptomyces venezuelae exhibits significant substrate tolerance and performs multiple hydroxylation reactions on structurally variant macrolides bearing the deoxyamino sugar desosamine. In previously determined co-crystal structures (Sherman, D. H., Li, S., Yermalitskaya, L. V., Kim, Y., Smith, J. A., Waterman, M. R., and Podust, L. M. (2006) J. Biol. Chem. 281, 26289-26297), the desosamine moiety of the native substrates YC-17 and narbomycin is bound in two distinct buried and surface-exposed binding pockets, mediated by specific interactions between the protonated dimethylamino group and the acidic amino acid residues Asp(50), Glu(85), and Glu(94). Although the Glu(85) and Glu(94) negative charges are essential for maximal catalytic activity of native enzyme, elimination of the surface-exposed negative charge at Asp(50) results in significantly enhanced catalytic activity. Nevertheless, the D50N substitution could not rescue catalytic activity of PikC(E94Q) based on lack of activity in the corresponding double mutant PikC(D50N/E94Q). To address the specific role for each desosamine-binding pocket, we analyzed the x-ray structures of the PikC(D50N) mutant co-crystallized with narbomycin (1.85A resolution) and YC-17 (3.2A resolution). In PikC(D50N), the desosamine moiety of both YC-17 and narbomycin was bound in a catalytically productive "buried site." This finding suggested a two-step substrate binding mechanism, whereby desosamine is recognized in the two subsites to allow the macrolide substrate to sequentially progress toward a catalytically favorable orientation. Collectively, the binding, mutagenesis, kinetic, and x-ray structural data suggest that enhancement of the catalytic activity of PikC(D50N) is due to the facilitated relocation of substrate to the buried site, which has higher binding affinity, as opposed to dissociation in solution from the transient "surface-exposed site."
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===CRYSTAL STRUCTURE OF THE NARBOMYCIN-BOUND PIKC D50N MUTANT===
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Analysis of transient and catalytic desosamine-binding pockets in cytochrome P-450 PikC from Streptomyces venezuelae.,Li S, Ouellet H, Sherman DH, Podust LM J Biol Chem. 2009 Feb 27;284(9):5723-30. Epub 2009 Jan 4. PMID:19124459<ref>PMID:19124459</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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The line below this paragraph, {{ABSTRACT_PUBMED_19124459}}, adds the Publication Abstract to the page
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<div class="pdbe-citations 2vzm" style="background-color:#fffaf0;"></div>
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(as it appears on PubMed at http://www.pubmed.gov), where 19124459 is the PubMed ID number.
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{{ABSTRACT_PUBMED_19124459}}
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==About this Structure==
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[[2vzm]] 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=2VZM 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:19124459</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: 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: 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: Pikc]]
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Current revision

Crystal structure of the narbomycin-bound PikC D50N mutant

PDB ID 2vzm

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