8Y11

Crystal structure of L-2-keto-3-deoxyfuconate 4-dehydrogenase bound to NAD(H) and sulfate ion

Summary for 8Y11

• Entry DOI: 10.2210/pdb8y11/pdb
• Descriptor: SDR family oxidoreductase, NICOTINAMIDE-ADENINE-DINUCLEOTIDE, SULFATE ION, ... (7 entities in total)
• Functional Keywords: dehydrogenase, rossmann fold, oxidoreductase
• Biological source: Herbaspirillum huttiense
• Total number of polymer chains: 4
• Total formula weight: 113884.75

Authors

Akagashi, M.,Watanabe, S. (deposition date: 2024-01-23, release date: 2024-07-10)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.77 Å)