2oam

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(New page: 200px<br /><applet load="2oam" size="350" color="white" frame="true" align="right" spinBox="true" caption="2oam, resolution 2.300&Aring;" /> '''Apo RebH from Leche...)
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[[Image:2oam.gif|left|200px]]<br /><applet load="2oam" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="2oam, resolution 2.300&Aring;" />
 
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'''Apo RebH from Lechevalieria aerocolonigenes'''<br />
 
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==Overview==
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==Apo RebH from Lechevalieria aerocolonigenes==
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The flavin-dependent halogenase RebH catalyzes the formation of, 7-chlorotryptophan as the initial step in the biosynthesis of antitumor, agent rebeccamycin. The reaction of FADH2, Cl-, and O2 in the active site, generates the powerful oxidant HOCl, which was presumed to carry out the, chlorination reaction. Herein, we demonstrate the formation of a, long-lived chlorinating intermediate (t1/2 = 63 h at 4 degrees C) when, RebH, FADH2, Cl-, and O2 react in the absence of substrate tryptophan., This intermediate remained on the enzyme after removal of FAD and, transferred chlorine to tryptophan with kinetically competent rates. The, identity of this intermediate is suggested by the X-ray crystal structure, of RebH, which revealed an active site Lys79 located in a central position, between flavin and tryptophan binding sites and just 4.1 A above C7 of, tryptophan. The chlorinating species is proposed to be a Lys-epsilonNH-Cl, (lysine chloramine) from reaction of enzyme-generated HOCl with the active, site Lys79. This covalent enzyme chloramine likely plays a key role in, directing regiospecific chlorination of substrate in this important class, of biosynthetic enzymes.
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<StructureSection load='2oam' size='340' side='right'caption='[[2oam]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2oam]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Lentzea_aerocolonigenes Lentzea aerocolonigenes]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2OAM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2OAM 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]] 2.3&#8491;</td></tr>
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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=2oam FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2oam OCA], [https://pdbe.org/2oam PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2oam RCSB], [https://www.ebi.ac.uk/pdbsum/2oam PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2oam ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/REBH_LENAE REBH_LENAE] Involved in the biosynthesis of the indolocarbazole antitumor agent rebeccamycin. Catalyzes the chlorination of tryptophan (Trp) at C7 position to yield 7-chlorotryptophan. The reaction between FADH2, Cl-, and O2 generates the powerful oxidant HOCl, which is presumed to carry out the chlorination reaction. The reaction of HOCl with the active site Lys-79 generates a lysine chloramine, which plays a key role in directing regiospecific chlorination of substrate in this important class of biosynthetic enzymes. It is also able to use bromide ions to generate monobrominated Trp.<ref>PMID:11983340</ref> <ref>PMID:15743914</ref> <ref>PMID:17260957</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/oa/2oam_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=2oam 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 flavin-dependent halogenase RebH catalyzes the formation of 7-chlorotryptophan as the initial step in the biosynthesis of antitumor agent rebeccamycin. The reaction of FADH2, Cl-, and O2 in the active site generates the powerful oxidant HOCl, which was presumed to carry out the chlorination reaction. Herein, we demonstrate the formation of a long-lived chlorinating intermediate (t1/2 = 63 h at 4 degrees C) when RebH, FADH2, Cl-, and O2 react in the absence of substrate tryptophan. This intermediate remained on the enzyme after removal of FAD and transferred chlorine to tryptophan with kinetically competent rates. The identity of this intermediate is suggested by the X-ray crystal structure of RebH, which revealed an active site Lys79 located in a central position between flavin and tryptophan binding sites and just 4.1 A above C7 of tryptophan. The chlorinating species is proposed to be a Lys-epsilonNH-Cl (lysine chloramine) from reaction of enzyme-generated HOCl with the active site Lys79. This covalent enzyme chloramine likely plays a key role in directing regiospecific chlorination of substrate in this important class of biosynthetic enzymes.
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==About this Structure==
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Chlorination by a long-lived intermediate in the mechanism of flavin-dependent halogenases.,Yeh E, Blasiak LC, Koglin A, Drennan CL, Walsh CT Biochemistry. 2007 Feb 6;46(5):1284-92. PMID:17260957<ref>PMID:17260957</ref>
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2OAM is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Lechevalieria_aerocolonigenes Lechevalieria aerocolonigenes]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2OAM OCA].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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Chlorination by a long-lived intermediate in the mechanism of flavin-dependent halogenases., Yeh E, Blasiak LC, Koglin A, Drennan CL, Walsh CT, Biochemistry. 2007 Feb 6;46(5):1284-92. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17260957 17260957]
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</div>
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[[Category: Lechevalieria aerocolonigenes]]
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<div class="pdbe-citations 2oam" style="background-color:#fffaf0;"></div>
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[[Category: Single protein]]
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== References ==
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[[Category: Blasiak, L.C.]]
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<references/>
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[[Category: Drennan, C.L.]]
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__TOC__
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[[Category: flavin-binding]]
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</StructureSection>
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[[Category: rebeccamycin biosynthesis]]
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[[Category: Large Structures]]
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[[Category: tryptophan-7-halogenase]]
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[[Category: Lentzea aerocolonigenes]]
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[[Category: Blasiak LC]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jan 29 21:08:02 2008''
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[[Category: Drennan CL]]

Current revision

Apo RebH from Lechevalieria aerocolonigenes

PDB ID 2oam

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