1R2J

FkbI for Biosynthesis of Methoxymalonyl Extender Unit of Fk520 Polyketide Immunosuppresant

1R2J の概要

• エントリーDOI: 10.2210/pdb1r2j/pdb
• 分子名称: protein FkbI, FLAVIN-ADENINE DINUCLEOTIDE (3 entities in total)
• 機能のキーワード: fk520; fk506; polyketide synthase; polyketide; acyl-coa dehydrogenase; crystal structure; aldehyde dehydrogenase, oxidoreductase
• 由来する生物種: Streptomyces hygroscopicus
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 39017.88

構造登録者

Watanabe, K.,Khosla, C.,Stroud, R.M.,Tsai, S.-C. (登録日: 2003-09-28, 公開日: 2003-11-25, 最終更新日: 2024-02-14)

主引用文献

Watanabe, K.,Khosla, C.,Stroud, R.M.,Tsai, S.-C.
Crystal Structure of an Acyl-ACP Dehydrogenase from the FK520 Polyketide Biosynthetic Pathway: Insights into Extender Unit Biosynthesis
J.Mol.Biol., 334:435-444, 2003

PubMed Abstract: 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.

PubMed: 14623185
DOI: 10.1016/j.jmb.2003.10.021

実験手法

X-RAY DIFFRACTION (2.1 Å)