6H0P

The structure of C100A mutant of Arabidopsis thaliana UDP-apiose/UDP-xylose synthase in complex with NADH and UDP-D-glucuronic acid

6H0P の概要

• エントリーDOI: 10.2210/pdb6h0p/pdb
• 分子名称: UDP-D-apiose/UDP-D-xylose synthase 1, NICOTINAMIDE-ADENINE-DINUCLEOTIDE, URIDINE-5'-DIPHOSPHATE-GLUCURONIC ACID (3 entities in total)
• 機能のキーワード: enzyme catalysis, glycobiology, short-chain dehydrogenases/reductases (sdr), aldol cleavage, substrate-assisted reaction, oxidoreductase
• 由来する生物種: Arabidopsis thaliana (Mouse-ear cress)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 89800.79

構造登録者

Savino, S.,Mattevi, A. (登録日: 2018-07-10, 公開日: 2019-10-23, 最終更新日: 2024-01-17)

主引用文献

Savino, S.,Borg, A.J.E.,Dennig, A.,Pfeiffer, M.,de Giorgi, F.,Weber, H.,Dubey, K.D.,Rovira, C.,Mattevi, A.,Nidetzky, B.
Deciphering the enzymatic mechanism of sugar ring contraction in UDP-apiose biosynthesis.
Nat Catal, 2:1115-1123, 2019

PubMed Abstract: D-Apiose is a -branched pentose sugar important for plant cell wall development. Its biosynthesis as UDP-D-apiose involves decarboxylation of the UDP-D-glucuronic acid precursor coupled to pyranosyl-to-furanosyl sugar ring contraction. This unusual multistep reaction is catalyzed within a single active site by UDP-D-apiose/UDP-D-xylose synthase (UAXS). Here, we decipher the UAXS catalytic mechanism based on crystal structures of the enzyme from , molecular dynamics simulations expanded by QM/MM calculations, and mutational-mechanistic analyses. Our studies show how UAXS uniquely integrates a classical catalytic cycle of oxidation and reduction by a tightly bound nicotinamide coenzyme with retro-aldol/aldol chemistry for the sugar ring contraction. They further demonstrate that decarboxylation occurs only after the sugar ring opening and identify the thiol group of Cys100 in steering the sugar skeleton rearrangement by proton transfer to and from the C3'. The mechanistic features of UAXS highlight the evolutionary expansion of the basic catalytic apparatus of short-chain dehydrogenases/reductases for functional versatility in sugar biosynthesis.

PubMed: 31844840
DOI: 10.1038/s41929-019-0382-8

実験手法

X-RAY DIFFRACTION (3.47 Å)