8Y4B

Crystal structure of L-2-keto-3-deoxyfuconate 4-dehydrogenase bound to L-2,4-DKDF and NADH

これはPDB形式変換不可エントリーです。

8Y4B の概要

• エントリーDOI: 10.2210/pdb8y4b/pdb
• 分子名称: SDR family oxidoreductase, NICOTINAMIDE-ADENINE-DINUCLEOTIDE, L-2,4-diketo-3-deoxyfuconate, ... (4 entities in total)
• 機能のキーワード: dehydrogenase, rossmann fold, oxidoreductase
• 由来する生物種: Herbaspirillum huttiense
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 113198.93

構造登録者

Akagashi, M.,Watanabe, S. (登録日: 2024-01-30, 公開日: 2024-07-10)

主引用文献

Akagashi, M.,Watanabe, S.,Kwiatkowski, S.,Drozak, J.,Terawaki, S.,Watanabe, Y.
Crystal structure of L-2-keto-3-deoxyfuconate 4-dehydrogenase reveals a unique binding mode as a alpha-furanosyl hemiketal of substrates.
Sci Rep, 14:14602-14602, 2024

PubMed Abstract: L-2-Keto-3-deoxyfuconate 4-dehydrogenase (L-KDFDH) catalyzes the NAD-dependent oxidization of L-2-keto-3-deoxyfuconate (L-KDF) to L-2,4-diketo-3-deoxyfuconate (L-2,4-DKDF) in the non-phosphorylating L-fucose pathway from bacteria, and its substrate was previously considered to be the acyclic α-keto form of L-KDF. On the other hand, BDH2, a mammalian homolog with L-KDFDH, functions as a dehydrogenase for cis-4-hydroxy-L-proline (C4LHyp) with the cyclic structure. We found that L-KDFDH and BDH2 utilize C4LHyp and L-KDF, respectively. Therefore, to elucidate unique substrate specificity at the atomic level, we herein investigated for the first time the crystal structures of L-KDFDH from Herbaspirillum huttiense in the ligand-free, L-KDF and L-2,4-DKDF, D-KDP (D-2-keto-3-deoxypentonate; additional substrate), or L-2,4-DKDF and NADH bound forms. In complexed structures, L-KDF, L-2,4-DKDF, and D-KDP commonly bound as a α-furanosyl hemiketal. Furthermore, L-KDFDH showed no activity for L-KDF and D-KDP analogs without the C5 hydroxyl group, which form only the acyclic α-keto form. The C1 carboxyl and α-anomeric C2 hydroxyl groups and O5 oxygen atom of the substrate (and product) were specifically recognized by Arg148, Arg192, and Arg214. The side chain of Trp252 was important for hydrophobically recognizing the C6 methyl group of L-KDF. This is the first example showing the physiological role of the hemiketal of 2-keto-3-deoxysugar acid.

PubMed: 38918500
DOI: 10.1038/s41598-024-65627-8

実験手法

X-RAY DIFFRACTION (1.67 Å)