1rqr
From Proteopedia
(New page: 200px<br /><applet load="1rqr" size="450" color="white" frame="true" align="right" spinBox="true" caption="1rqr, resolution 2.67Å" /> '''Crystal structure an...) |
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| - | [[Image:1rqr.gif|left|200px]]<br /><applet load="1rqr" size=" | + | [[Image:1rqr.gif|left|200px]]<br /><applet load="1rqr" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1rqr, resolution 2.67Å" /> | caption="1rqr, resolution 2.67Å" /> | ||
'''Crystal structure and mechanism of a bacterial fluorinating enzyme, product complex'''<br /> | '''Crystal structure and mechanism of a bacterial fluorinating enzyme, product complex'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Fluorine is the thirteenth most abundant element in the earth's crust, but | + | 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== | ==About this Structure== | ||
| - | 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:// | + | 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 <scene name='pdbligand=5FD:'>5FD</scene> and <scene name='pdbligand=MET:'>MET</scene> 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://oca.weizmann.ac.il/oca-bin/ocashort?id=1RQR OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Deng, H.]] | [[Category: Deng, H.]] | ||
[[Category: Dong, C.]] | [[Category: Dong, C.]] | ||
| - | [[Category: Hagan, D | + | [[Category: Hagan, D O.]] |
[[Category: Huang, F.]] | [[Category: Huang, F.]] | ||
| - | [[Category: Naismith, J | + | [[Category: Naismith, J H.]] |
[[Category: Schaffrath, C.]] | [[Category: Schaffrath, C.]] | ||
| - | [[Category: Spencer, J | + | [[Category: Spencer, J B.]] |
[[Category: 5FD]] | [[Category: 5FD]] | ||
[[Category: MET]] | [[Category: MET]] | ||
| Line 27: | Line 27: | ||
[[Category: fluorinase]] | [[Category: fluorinase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:53:37 2008'' |
Revision as of 12:53, 21 February 2008
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Crystal structure and mechanism of a bacterial fluorinating enzyme, product complex
Overview
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
1RQR is a Single protein structure of sequence from Streptomyces cattleya with and as ligands. Active as Adenosyl-fluoride synthase, with EC number 2.5.1.63 Full crystallographic information is available from OCA.
Reference
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
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