1r2j
From Proteopedia
(New page: 200px<br /><applet load="1r2j" size="450" color="white" frame="true" align="right" spinBox="true" caption="1r2j, resolution 2.10Å" /> '''FkbI for Biosynthesi...) |
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| - | [[Image:1r2j.gif|left|200px]]<br /><applet load="1r2j" size=" | + | [[Image:1r2j.gif|left|200px]]<br /><applet load="1r2j" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1r2j, resolution 2.10Å" /> | caption="1r2j, resolution 2.10Å" /> | ||
'''FkbI for Biosynthesis of Methoxymalonyl Extender Unit of Fk520 Polyketide Immunosuppresant'''<br /> | '''FkbI for Biosynthesis of Methoxymalonyl Extender Unit of Fk520 Polyketide Immunosuppresant'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Polyketide synthases (PKSs) synthesize the polyketide cores of | + | Polyketide synthases (PKSs) synthesize the polyketide cores of pharmacologically important natural products such as the immunosuppressants FK520 and FK506. Understanding polyketide biosynthesis at atomic resolution could present new opportunities for chemo-enzymatic synthesis of complex molecules. The crystal structure of FkbI, an enzyme involved in the biosynthesis of the methoxymalonyl extender unit of FK520, was solved to 2.1A with an R(crys) of 24.4%. FkbI has a similar fold to acyl-CoA dehydrogenases. Notwithstanding this similarity, the surface and substrate-binding site of FkbI reveal key differences from other acyl-CoA dehydrogenases, suggesting that FkbI may recognize an acyl-ACP substrate rather than an acyl-CoA substrate. This structural observation coincided the genetic experiment done by Carroll et al. J. Am. Chem. Soc., 124 (2002) 4176. Although an in vitro assay for FkbI remains elusive, the structural basis for the substrate specificity of FkbI is analyzed by a combination of sequence comparison, docking simulations and structural analysis. A biochemical mechanism for the role of FkbI in the biosynthesis of methoxymalonyl-ACP is proposed. |
==About this Structure== | ==About this Structure== | ||
| - | 1R2J is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Streptomyces_hygroscopicus Streptomyces hygroscopicus] with FAD as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1R2J is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Streptomyces_hygroscopicus Streptomyces hygroscopicus] with <scene name='pdbligand=FAD:'>FAD</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1R2J OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Streptomyces hygroscopicus]] | [[Category: Streptomyces hygroscopicus]] | ||
[[Category: Khosla, C.]] | [[Category: Khosla, C.]] | ||
| - | [[Category: Stroud, R | + | [[Category: Stroud, R M.]] |
| - | [[Category: Tsai, S | + | [[Category: Tsai, S C.]] |
[[Category: Watanabe, K.]] | [[Category: Watanabe, K.]] | ||
[[Category: FAD]] | [[Category: FAD]] | ||
[[Category: fk520; fk506; polyketide synthase; polyketide; acyl-coa dehydrogenase; crystal structure; aldehyde dehydrogenase]] | [[Category: fk520; fk506; polyketide synthase; polyketide; acyl-coa dehydrogenase; crystal structure; aldehyde dehydrogenase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:46:20 2008'' |
Revision as of 12:46, 21 February 2008
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FkbI for Biosynthesis of Methoxymalonyl Extender Unit of Fk520 Polyketide Immunosuppresant
Overview
Polyketide synthases (PKSs) synthesize the polyketide cores of pharmacologically important natural products such as the immunosuppressants FK520 and FK506. Understanding polyketide biosynthesis at atomic resolution could present new opportunities for chemo-enzymatic synthesis of complex molecules. The crystal structure of FkbI, an enzyme involved in the biosynthesis of the methoxymalonyl extender unit of FK520, was solved to 2.1A with an R(crys) of 24.4%. FkbI has a similar fold to acyl-CoA dehydrogenases. Notwithstanding this similarity, the surface and substrate-binding site of FkbI reveal key differences from other acyl-CoA dehydrogenases, suggesting that FkbI may recognize an acyl-ACP substrate rather than an acyl-CoA substrate. This structural observation coincided the genetic experiment done by Carroll et al. J. Am. Chem. Soc., 124 (2002) 4176. Although an in vitro assay for FkbI remains elusive, the structural basis for the substrate specificity of FkbI is analyzed by a combination of sequence comparison, docking simulations and structural analysis. A biochemical mechanism for the role of FkbI in the biosynthesis of methoxymalonyl-ACP is proposed.
About this Structure
1R2J is a Single protein structure of sequence from Streptomyces hygroscopicus with as ligand. Full crystallographic information is available from OCA.
Reference
Crystal structure of an Acyl-ACP dehydrogenase from the FK520 polyketide biosynthetic pathway: insights into extender unit biosynthesis., Watanabe K, Khosla C, Stroud RM, Tsai SC, J Mol Biol. 2003 Nov 28;334(3):435-44. PMID:14623185
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