2h7x

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{{Seed}}
 
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[[Image:2h7x.png|left|200px]]
 
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==Pikromycin Thioesterase adduct with reduced triketide affinity label==
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The line below this paragraph, containing "STRUCTURE_2h7x", creates the "Structure Box" on the page.
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<StructureSection load='2h7x' size='340' side='right'caption='[[2h7x]], [[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'>[[2h7x]] 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=2H7X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2H7X 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]] 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=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PSX:[(2S,3R,4S)-2,4-DIHYDROXY-3-METHYLHEXYL]PHOSPHONIC+ACID'>PSX</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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{{STRUCTURE_2h7x| PDB=2h7x | 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=2h7x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2h7x OCA], [https://pdbe.org/2h7x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2h7x RCSB], [https://www.ebi.ac.uk/pdbsum/2h7x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2h7x ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/PIKA4_STRVZ PIKA4_STRVZ] Involved in the biosynthesis of 12- and 14-membered ring macrolactone antibiotics such as methymycin and neomethymycin, and pikromycin and narbomycin, respectively. Component of the pikromycin PKS which catalyzes the biosynthesis of both precursors 10-deoxymethynolide (12-membered ring macrolactone) and narbonolide (14-membered ring macrolactone). Chain elongation through PikAI, PikAII and PikAIII followed by thioesterase catalyzed termination results in the production of 10-deoxymethynolide, while continued elongation through PikAIV, followed by thioesterase (TE) catalyzed cyclization results in the biosynthesis of the narbonolide. The thioesterase can use a series of diketide-N-acetylcysteamine (SNAC) thioesters, but has a strong preference for the 2-methyl-3-ketopentanoyl-SNAC over the stereoisomers of 2-methyl-3-hydroxyacyl-SNAC (PubMed:12379101, PubMed:12733905).<ref>PMID:10421766</ref> <ref>PMID:10676969</ref> <ref>PMID:12379101</ref> <ref>PMID:12733905</ref> <ref>PMID:16969372</ref> <ref>PMID:17719493</ref> <ref>PMID:19027305</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/h7/2h7x_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=2h7x 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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Polyketides are a diverse class of natural products having important clinical properties, including antibiotic, immunosuppressive and anticancer activities. They are biosynthesized by polyketide synthases (PKSs), which are modular, multienzyme complexes that sequentially condense simple carboxylic acid derivatives. The final reaction in many PKSs involves thioesterase-catalyzed cyclization of linear chain elongation intermediates. As the substrate in PKSs is presented by a tethered acyl carrier protein, introduction of substrate by diffusion is problematic, and no substrate-bound type I PKS domain structure has been reported so far. We describe the chemical synthesis of polyketide-based affinity labels that covalently modify the active site serine of excised pikromycin thioesterase from Streptomyces venezuelae. Crystal structures reported here of the affinity label-pikromycin thioesterase adducts provide important mechanistic insights. These results suggest that affinity labels can be valuable tools for understanding the mechanisms of individual steps within multifunctional PKSs and for directing rational engineering of PKS domains for combinatorial biosynthesis.
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===Pikromycin Thioesterase adduct with reduced triketide affinity label===
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Structural and mechanistic insights into polyketide macrolactonization from polyketide-based affinity labels.,Giraldes JW, Akey DL, Kittendorf JD, Sherman DH, Smith JL, Fecik RA Nat Chem Biol. 2006 Oct;2(10):531-6. Epub 2006 Sep 10. PMID:16969373<ref>PMID:16969373</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>
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The line below this paragraph, {{ABSTRACT_PUBMED_16969373}}, adds the Publication Abstract to the page
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<div class="pdbe-citations 2h7x" style="background-color:#fffaf0;"></div>
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(as it appears on PubMed at http://www.pubmed.gov), where 16969373 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_16969373}}
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__TOC__
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</StructureSection>
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==About this Structure==
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[[Category: Large Structures]]
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2H7X is a 2 chains structure of sequences 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=2H7X OCA].
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==Reference==
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<ref group="xtra">PMID:16969373</ref><references group="xtra"/>
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[[Category: Streptomyces venezuelae]]
[[Category: Streptomyces venezuelae]]
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[[Category: Akey, D L.]]
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[[Category: Akey DL]]
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[[Category: Fecik, R A.]]
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[[Category: Fecik RA]]
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[[Category: Giraldes, J W.]]
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[[Category: Giraldes JW]]
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[[Category: Kittendorf, J D.]]
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[[Category: Kittendorf JD]]
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[[Category: Sherman, D H.]]
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[[Category: Sherman DH]]
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[[Category: Smith, J S.]]
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[[Category: Smith JS]]
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[[Category: Alpha-beta hydrolase]]
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[[Category: Thioesterase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Feb 18 02:35:36 2009''
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Current revision

Pikromycin Thioesterase adduct with reduced triketide affinity label

PDB ID 2h7x

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