6CXT

Crystal structure of FAD-dependent dehydrogenase

6CXT の概要

• エントリーDOI: 10.2210/pdb6cxt/pdb
• 分子名称: Alpha/beta hydrolase fold protein, Butyryl-CoA dehydrogenase, S-[2-({N-[(2R)-2-hydroxy-4-{[(R)-hydroxy(oxo)-lambda~5~-phosphanyl]oxy}-3,3-dimethylbutanoyl]-beta-alanyl}amino)ethyl] 1H-pyrrole-2-carbothioate, ... (6 entities in total)
• 機能のキーワード: acyl carrier protein, fad-dependent enzyme, natural product biosynthesis, oxidoreductase
• 由来する生物種: Marinomonas mediterranea (strain ATCC 700492 / JCM 21426 / NBRC 103028 / MMB-1); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 51641.79

構造登録者

Agarwal, V. (登録日: 2018-04-04, 公開日: 2019-01-16, 最終更新日: 2024-11-13)

主引用文献

Thapa, H.R.,Robbins, J.M.,Moore, B.S.,Agarwal, V.
Insights into Thiotemplated Pyrrole Biosynthesis Gained from the Crystal Structure of Flavin-Dependent Oxidase in Complex with Carrier Protein.
Biochemistry, 58:918-929, 2019

PubMed Abstract: Sequential enzymatic reactions on substrates tethered to carrier proteins (CPs) generate thiotemplated building blocks that are then delivered to nonribosomal peptide synthetases (NRPSs) to generate peptidic natural products. The underlying diversity of these thiotemplated building blocks is the principal driver of the chemical diversity of NRPS-derived natural products. Structural insights into recognition of CPs by tailoring enzymes that generate these building blocks are sparse. Here we present the crystal structure of a flavin-dependent prolyl oxidase that furnishes thiotemplated pyrrole as the product, in complex with its cognate CP in the holo and product-bound states. The thiotemplated pyrrole is an intermediate that is well-represented in natural product biosynthetic pathways. Our results delineate the interactions between the CP and the oxidase while also providing insights into the stereospecificity of the enzymatic oxidation of the prolyl heterocycle to the aromatic pyrrole. Biochemical validation of the interaction between the CP and the oxidase demonstrates that NRPSs recognize and bind to their CPs using interactions quite different from those of fatty acid and polyketide biosynthetic enzymes. Our results posit that structural diversity in natural product biosynthesis can be, and is, derived from subtle modifications of primary metabolic enzymes.

PubMed: 30620182
DOI: 10.1021/acs.biochem.8b01177

実験手法

X-RAY DIFFRACTION (1.9 Å)