2r0c
From Proteopedia
(New page: 200px<br /><applet load="2r0c" size="350" color="white" frame="true" align="right" spinBox="true" caption="2r0c, resolution 1.80Å" /> '''Structure of the sub...) |
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==Overview== | ==Overview== | ||
| - | The biosynthesis of rebeccamycin, an antitumor compound, involves the | + | The biosynthesis of rebeccamycin, an antitumor compound, involves the remarkable eight-electron oxidation of chlorinated chromopyrrolic acid. Although one rebeccamycin biosynthetic enzyme is capable of generating low levels of the eight-electron oxidation product on its own, a second protein, RebC, is required to accelerate product formation and eliminate side reactions. However, the mode of action of RebC was largely unknown. Using crystallography, we have determined a likely function for RebC as a flavin hydroxylase, captured two snapshots of its dynamic catalytic cycle, and trapped a reactive molecule, a putative substrate, in its binding pocket. These studies strongly suggest that the role of RebC is to sequester a reactive intermediate produced by its partner protein and to react with it enzymatically, preventing its conversion to a suite of degradation products that includes, at low levels, the desired product. |
==About this Structure== | ==About this Structure== | ||
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==Reference== | ==Reference== | ||
| - | Crystallographic trapping in the rebeccamycin biosynthetic enzyme RebC., Ryan KS, Howard-Jones AR, Hamill MJ, Elliott SJ, Walsh CT, Drennan CL, Proc Natl Acad Sci U S A. 2007 Sep | + | Crystallographic trapping in the rebeccamycin biosynthetic enzyme RebC., Ryan KS, Howard-Jones AR, Hamill MJ, Elliott SJ, Walsh CT, Drennan CL, Proc Natl Acad Sci U S A. 2007 Sep 25;104(39):15311-6. Epub 2007 Sep 14. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17873060 17873060] |
[[Category: Lechevalieria aerocolonigenes]] | [[Category: Lechevalieria aerocolonigenes]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Drennan, C | + | [[Category: Drennan, C L.]] |
| - | [[Category: Ryan, K | + | [[Category: Ryan, K S.]] |
[[Category: CL]] | [[Category: CL]] | ||
[[Category: FAD]] | [[Category: FAD]] | ||
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[[Category: oxidoreductase]] | [[Category: oxidoreductase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:43:40 2008'' |
Revision as of 16:43, 21 February 2008
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Structure of the substrate-free form of the rebeccamycin biosynthetic enzyme REBC
Overview
The biosynthesis of rebeccamycin, an antitumor compound, involves the remarkable eight-electron oxidation of chlorinated chromopyrrolic acid. Although one rebeccamycin biosynthetic enzyme is capable of generating low levels of the eight-electron oxidation product on its own, a second protein, RebC, is required to accelerate product formation and eliminate side reactions. However, the mode of action of RebC was largely unknown. Using crystallography, we have determined a likely function for RebC as a flavin hydroxylase, captured two snapshots of its dynamic catalytic cycle, and trapped a reactive molecule, a putative substrate, in its binding pocket. These studies strongly suggest that the role of RebC is to sequester a reactive intermediate produced by its partner protein and to react with it enzymatically, preventing its conversion to a suite of degradation products that includes, at low levels, the desired product.
About this Structure
2R0C is a Single protein structure of sequence from Lechevalieria aerocolonigenes with and as ligands. Full crystallographic information is available from OCA.
Reference
Crystallographic trapping in the rebeccamycin biosynthetic enzyme RebC., Ryan KS, Howard-Jones AR, Hamill MJ, Elliott SJ, Walsh CT, Drennan CL, Proc Natl Acad Sci U S A. 2007 Sep 25;104(39):15311-6. Epub 2007 Sep 14. PMID:17873060
Page seeded by OCA on Thu Feb 21 18:43:40 2008
