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| - | [[Image:1rqr.gif|left|200px]]<br /><applet load="1rqr" size="450" color="white" frame="true" align="right" spinBox="true" | |
| - | caption="1rqr, resolution 2.67Å" /> | |
| - | '''Crystal structure and mechanism of a bacterial fluorinating enzyme, product complex'''<br /> | |
| | | | |
| - | ==Overview== | + | ==Crystal structure and mechanism of a bacterial fluorinating enzyme, product complex== |
| - | Fluorine is the thirteenth most abundant element in the earth's crust, but, fluoride concentrations in surface water are low and fluorinated, metabolites are extremely rare. The fluoride ion is a potent nucleophile, in its desolvated state, but is tightly hydrated in water and effectively, inert. Low availability and a lack of chemical reactivity have largely, excluded fluoride from biochemistry: in particular, fluorine's high redox, potential precludes the haloperoxidase-type mechanism used in the, metabolic incorporation of chloride and bromide ions. But fluorinated, chemicals are growing in industrial importance, with applications in, pharmaceuticals, agrochemicals and materials products. Reactive, fluorination reagents requiring specialist process technologies are needed, in industry and, although biological catalysts for these processes are, highly sought after, only one enzyme that can convert fluoride to organic, fluorine has been described. Streptomyces cattleya can form, carbon-fluorine bonds and must therefore have evolved an enzyme able to, overcome the chemical challenges of using aqueous fluoride. Here we report, the sequence and three-dimensional structure of the first native, fluorination enzyme, 5'-fluoro-5'-deoxyadenosine synthase, from this, organism. Both substrate and products have been observed bound to the, enzyme, enabling us to propose a nucleophilic substitution mechanism for, this biological fluorination reaction. | + | <StructureSection load='1rqr' size='340' side='right'caption='[[1rqr]], [[Resolution|resolution]] 2.67Å' scene=''> |
| | + | == Structural highlights == |
| | + | <table><tr><td colspan='2'>[[1rqr]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptomyces_cattleya Streptomyces cattleya]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1RQR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1RQR FirstGlance]. <br> |
| | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.67Å</td></tr> |
| | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5FD:5-FLUORO-5-DEOXYADENOSINE'>5FD</scene>, <scene name='pdbligand=MET:METHIONINE'>MET</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</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=1rqr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1rqr OCA], [https://pdbe.org/1rqr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1rqr RCSB], [https://www.ebi.ac.uk/pdbsum/1rqr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1rqr ProSAT]</span></td></tr> |
| | + | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/FLA_STRCT FLA_STRCT] Involved in the biosynthesis of fluorometabolites. Catalyzes the formation of a C-F bond by combining S-adenosyl-L-methionine (SAM) and fluoride to generate 5'-fluoro-5'-deoxyadenosine (5'-FDA) and L-methionine. It can also use 2'-deoxyadenosine in place of adenosine as substrate.<ref>PMID:12860396</ref> <ref>PMID:14765200</ref> <ref>PMID:16370017</ref> <ref>PMID:16604208</ref> <ref>PMID:16720268</ref> <ref>PMID:17985882</ref> |
| | + | == Evolutionary Conservation == |
| | + | [[Image:Consurf_key_small.gif|200px|right]] |
| | + | Check<jmol> |
| | + | <jmolCheckbox> |
| | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/rq/1rqr_consurf.spt"</scriptWhenChecked> |
| | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> |
| | + | <text>to colour the structure by Evolutionary Conservation</text> |
| | + | </jmolCheckbox> |
| | + | </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=1rqr ConSurf]. |
| | + | <div style="clear:both"></div> |
| | + | <div style="background-color:#fffaf0;"> |
| | + | == Publication Abstract from PubMed == |
| | + | Fluorine is the thirteenth most abundant element in the earth's crust, but fluoride concentrations in surface water are low and fluorinated metabolites are extremely rare. The fluoride ion is a potent nucleophile in its desolvated state, but is tightly hydrated in water and effectively inert. Low availability and a lack of chemical reactivity have largely excluded fluoride from biochemistry: in particular, fluorine's high redox potential precludes the haloperoxidase-type mechanism used in the metabolic incorporation of chloride and bromide ions. But fluorinated chemicals are growing in industrial importance, with applications in pharmaceuticals, agrochemicals and materials products. Reactive fluorination reagents requiring specialist process technologies are needed in industry and, although biological catalysts for these processes are highly sought after, only one enzyme that can convert fluoride to organic fluorine has been described. Streptomyces cattleya can form carbon-fluorine bonds and must therefore have evolved an enzyme able to overcome the chemical challenges of using aqueous fluoride. Here we report the sequence and three-dimensional structure of the first native fluorination enzyme, 5'-fluoro-5'-deoxyadenosine synthase, from this organism. Both substrate and products have been observed bound to the enzyme, enabling us to propose a nucleophilic substitution mechanism for this biological fluorination reaction. |
| | | | |
| - | ==About this Structure==
| + | Crystal structure and mechanism of a bacterial fluorinating enzyme.,Dong C, Huang F, Deng H, Schaffrath C, Spencer JB, O'Hagan D, Naismith JH Nature. 2004 Feb 5;427(6974):561-5. PMID:14765200<ref>PMID:14765200</ref> |
| - | 1RQR is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Streptomyces_cattleya Streptomyces cattleya] with 5FD and MET as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Adenosyl-fluoride_synthase Adenosyl-fluoride synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.5.1.63 2.5.1.63] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1RQR OCA].
| + | |
| | | | |
| - | ==Reference==
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| - | Crystal structure and mechanism of a bacterial fluorinating enzyme., Dong C, Huang F, Deng H, Schaffrath C, Spencer JB, O'Hagan D, Naismith JH, Nature. 2004 Feb 5;427(6974):561-5. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=14765200 14765200]
| + | </div> |
| - | [[Category: Adenosyl-fluoride synthase]]
| + | <div class="pdbe-citations 1rqr" style="background-color:#fffaf0;"></div> |
| - | [[Category: Single protein]] | + | == References == |
| | + | <references/> |
| | + | __TOC__ |
| | + | </StructureSection> |
| | + | [[Category: Large Structures]] |
| | [[Category: Streptomyces cattleya]] | | [[Category: Streptomyces cattleya]] |
| - | [[Category: Deng, H.]] | + | [[Category: Deng H]] |
| - | [[Category: Dong, C.]] | + | [[Category: Dong C]] |
| - | [[Category: Hagan, D.O.]] | + | [[Category: Huang F]] |
| - | [[Category: Huang, F.]] | + | [[Category: Naismith JH]] |
| - | [[Category: Naismith, J.H.]] | + | [[Category: O'Hagan D]] |
| - | [[Category: Schaffrath, C.]] | + | [[Category: Schaffrath C]] |
| - | [[Category: Spencer, J.B.]] | + | [[Category: Spencer JB]] |
| - | [[Category: 5FD]]
| + | |
| - | [[Category: MET]]
| + | |
| - | [[Category: anti-parallel beta sheets]]
| + | |
| - | [[Category: central 7 stranded beta sheets]]
| + | |
| - | [[Category: fluorinase]]
| + | |
| - | | + | |
| - | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Sat Nov 24 23:07:00 2007''
| + | |
| Structural highlights
Function
FLA_STRCT Involved in the biosynthesis of fluorometabolites. Catalyzes the formation of a C-F bond by combining S-adenosyl-L-methionine (SAM) and fluoride to generate 5'-fluoro-5'-deoxyadenosine (5'-FDA) and L-methionine. It can also use 2'-deoxyadenosine in place of adenosine as substrate.[1] [2] [3] [4] [5] [6]
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
Fluorine is the thirteenth most abundant element in the earth's crust, but fluoride concentrations in surface water are low and fluorinated metabolites are extremely rare. The fluoride ion is a potent nucleophile in its desolvated state, but is tightly hydrated in water and effectively inert. Low availability and a lack of chemical reactivity have largely excluded fluoride from biochemistry: in particular, fluorine's high redox potential precludes the haloperoxidase-type mechanism used in the metabolic incorporation of chloride and bromide ions. But fluorinated chemicals are growing in industrial importance, with applications in pharmaceuticals, agrochemicals and materials products. Reactive fluorination reagents requiring specialist process technologies are needed in industry and, although biological catalysts for these processes are highly sought after, only one enzyme that can convert fluoride to organic fluorine has been described. Streptomyces cattleya can form carbon-fluorine bonds and must therefore have evolved an enzyme able to overcome the chemical challenges of using aqueous fluoride. Here we report the sequence and three-dimensional structure of the first native fluorination enzyme, 5'-fluoro-5'-deoxyadenosine synthase, from this organism. Both substrate and products have been observed bound to the enzyme, enabling us to propose a nucleophilic substitution mechanism for this biological fluorination reaction.
Crystal structure and mechanism of a bacterial fluorinating enzyme.,Dong C, Huang F, Deng H, Schaffrath C, Spencer JB, O'Hagan D, Naismith JH Nature. 2004 Feb 5;427(6974):561-5. PMID:14765200[7]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Schaffrath C, Deng H, O'Hagan D. Isolation and characterisation of 5'-fluorodeoxyadenosine synthase, a fluorination enzyme from Streptomyces cattleya. FEBS Lett. 2003 Jul 17;547(1-3):111-4. PMID:12860396
- ↑ Dong C, Huang F, Deng H, Schaffrath C, Spencer JB, O'Hagan D, Naismith JH. Crystal structure and mechanism of a bacterial fluorinating enzyme. Nature. 2004 Feb 5;427(6974):561-5. PMID:14765200 doi:http://dx.doi.org/10.1038/nature02280
- ↑ Deng H, Cobb SL, McEwan AR, McGlinchey RP, Naismith JH, O'Hagan D, Robinson DA, Spencer JB. The fluorinase from Streptomyces cattleya is also a chlorinase. Angew Chem Int Ed Engl. 2006 Jan 23;45(5):759-62. PMID:16370017 doi:http://dx.doi.org/10.1002/anie.200503582
- ↑ Cobb SL, Deng H, McEwan AR, Naismith JH, O'Hagan D, Robinson DA. Substrate specificity in enzymatic fluorination. The fluorinase from Streptomyces cattleya accepts 2'-deoxyadenosine substrates. Org Biomol Chem. 2006 Apr 21;4(8):1458-60. Epub 2006 Mar 8. PMID:16604208 doi:10.1039/b600574h
- ↑ Huang F, Haydock SF, Spiteller D, Mironenko T, Li TL, O'Hagan D, Leadlay PF, Spencer JB. The gene cluster for fluorometabolite biosynthesis in Streptomyces cattleya: a thioesterase confers resistance to fluoroacetyl-coenzyme A. Chem Biol. 2006 May;13(5):475-84. PMID:16720268 doi:http://dx.doi.org/S1074-5521(06)00084-6
- ↑ Zhu X, Robinson DA, McEwan AR, O'Hagan D, Naismith JH. Mechanism of enzymatic fluorination in Streptomyces cattleya. J Am Chem Soc. 2007 Nov 28;129(47):14597-604. Epub 2007 Nov 7. PMID:17985882 doi:10.1021/ja0731569
- ↑ Dong C, Huang F, Deng H, Schaffrath C, Spencer JB, O'Hagan D, Naismith JH. Crystal structure and mechanism of a bacterial fluorinating enzyme. Nature. 2004 Feb 5;427(6974):561-5. PMID:14765200 doi:http://dx.doi.org/10.1038/nature02280
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