1r2j
From Proteopedia
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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 FAD 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
Page seeded by OCA on Sat Nov 24 21:58:48 2007
