6H0N

The structure of wild-type Arabidopsis thaliana UDP-apiose/UDP-xylose synthase in complex with NAD+ and UDP

Summary for 6H0N

• Entry DOI: 10.2210/pdb6h0n/pdb
• Descriptor: UDP-D-apiose/UDP-D-xylose synthase 1, NICOTINAMIDE-ADENINE-DINUCLEOTIDE, URIDINE-5'-DIPHOSPHATE, ... (5 entities in total)
• Functional Keywords: enzyme catalysis, glycobiology, short-chain dehydrogenases/reductases (sdr), aldol cleavage, substrate-assisted reaction, oxidoreductase
• Biological source: Arabidopsis thaliana (thale cress)
• Total number of polymer chains: 2
• Total formula weight: 89702.61

Authors

Savino, S.,Mattevi, A. (deposition date: 2018-07-10, release date: 2019-10-23, Last modification date: 2024-01-17)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (3.02 Å)