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| | <StructureSection load='3i3l' size='340' side='right'caption='[[3i3l]], [[Resolution|resolution]] 2.20Å' scene=''> | | <StructureSection load='3i3l' size='340' side='right'caption='[[3i3l]], [[Resolution|resolution]] 2.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3i3l]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/As_4.1526 As 4.1526]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3I3L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3I3L FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3i3l]] is a 1 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=3I3L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3I3L FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">cmlS ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=54571 AS 4.1526])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</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=3i3l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3i3l OCA], [https://pdbe.org/3i3l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3i3l RCSB], [https://www.ebi.ac.uk/pdbsum/3i3l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3i3l ProSAT]</span></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=3i3l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3i3l OCA], [https://pdbe.org/3i3l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3i3l RCSB], [https://www.ebi.ac.uk/pdbsum/3i3l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3i3l ProSAT]</span></td></tr> |
| | </table> | | </table> |
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| | <jmolCheckbox> | | <jmolCheckbox> |
| | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/i3/3i3l_consurf.spt"</scriptWhenChecked> | | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/i3/3i3l_consurf.spt"</scriptWhenChecked> |
| - | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> | | </jmolCheckbox> |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: As 4 1526]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Structural genomic]] | + | [[Category: Streptomyces venezuelae]] |
| - | [[Category: Jia, Z]] | + | [[Category: Jia Z]] |
| - | [[Category: Podzelinska, K]] | + | [[Category: Podzelinska K]] |
| - | [[Category: Soares, A]] | + | [[Category: Soares A]] |
| - | [[Category: Bsgi]]
| + | |
| - | [[Category: Chloramphenicol biosynthesis]]
| + | |
| - | [[Category: Cml]]
| + | |
| - | [[Category: Flavin-dependent halogenase]]
| + | |
| - | [[Category: Halogenation reaction]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| Structural highlights
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Chloramphenicol is a halogenated natural product bearing an unusual dichloroacetyl moiety that is critical for its antibiotic activity. The operon for chloramphenicol biosynthesis in Streptomyces venezuelae encodes the chloramphenicol halogenase CmlS, which belongs to the large and diverse family of flavin-dependent halogenases (FDH's). CmlS was previously shown to be essential for the formation of the dichloroacetyl group. Here we report the X-ray crystal structure of CmlS determined at 2.2 A resolution, revealing a flavin monooxygenase domain shared by all FDHs, but also a unique 'winged-helix' C-terminal domain that creates a T-shaped tunnel leading to the halogenation active site. Intriguingly, the C-terminal tail of this domain blocks access to the halogenation active site, suggesting a structurally dynamic role during catalysis. The halogenation active site is notably nonpolar and shares nearly identical residues with Chondromyces crocatus tyrosyl halogenase (CndH), including the conserved Lys (K71) that forms the reactive chloramine intermediate. The exception is Y350, which could be used to stabilize enolate formation during substrate halogenation. The strictly conserved residue E44, located near the isoalloxazine ring of the bound flavin adenine dinucleotide (FAD) cofactor, is optimally positioned to function as a remote general acid, through a water-mediated proton relay, which could accelerate the reaction of the chloramine intermediate during substrate halogenation, or the oxidation of chloride by the FAD(C4alpha)-OOH intermediate. Strikingly, the 8alpha carbon of the FAD cofactor is observed to be covalently attached to D277 of CmlS, a residue that is highly conserved in the FDH family. In addition to representing a new type of flavin modification, this has intriguing implications for the mechanism of FDHs. Based on the crystal structure and in analogy to known halogenases, we propose a reaction mechanism for CmlS.
Chloramphenicol biosynthesis: the structure of CmlS, a flavin-dependent halogenase showing a covalent flavin-aspartate bond.,Podzelinska K, Latimer R, Bhattacharya A, Vining LC, Zechel DL, Jia Z J Mol Biol. 2010 Mar 19;397(1):316-31. Epub 2010 Jan 18. PMID:20080101[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Podzelinska K, Latimer R, Bhattacharya A, Vining LC, Zechel DL, Jia Z. Chloramphenicol biosynthesis: the structure of CmlS, a flavin-dependent halogenase showing a covalent flavin-aspartate bond. J Mol Biol. 2010 Mar 19;397(1):316-31. Epub 2010 Jan 18. PMID:20080101 doi:10.1016/j.jmb.2010.01.020
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