9AZO

Crystal structure of CHMS Dehydrogenase PmdC from Comamonas testosteroni bound to cofactor NADP

9AZO の概要

• エントリーDOI: 10.2210/pdb9azo/pdb
• 分子名称: PmdC, SULFATE ION, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, ... (4 entities in total)
• 機能のキーワード: oxidoreductase, nadp cofactor, pyrone dicarboxylic acid, lignin degradation
• 由来する生物種: Comamonas testosteroni ATCC 11996
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 216638.52

構造登録者

Rodrigues, A.V.,Moriarty, N.W.,Pereira, J.H.,Adams, P.D. (登録日: 2024-03-11, 公開日: 2024-09-18, 最終更新日: 2024-10-16)

主引用文献

Rodrigues, A.V.,Moriarty, N.W.,Kakumanu, R.,DeGiovanni, A.,Pereira, J.H.,Gin, J.W.,Chen, Y.,Baidoo, E.E.K.,Petzold, C.J.,Adams, P.D.
Characterization of lignin-degrading enzyme PmdC, which catalyzes a key step in the synthesis of polymer precursor 2-pyrone-4,6-dicarboxylic acid.
J.Biol.Chem., 300:107736-107736, 2024

PubMed Abstract: Pyrone-2,4-dicarboxylic acid (PDC) is a valuable polymer precursor that can be derived from the microbial degradation of lignin. The key enzyme in the microbial production of PDC is 4-carboxy-2-hydroxymuconate-6-semialdehyde (CHMS) dehydrogenase, which acts on the substrate CHMS. We present the crystal structure of CHMS dehydrogenase (PmdC from Comamonas testosteroni) bound to the cofactor NADP, shedding light on its three-dimensional architecture, and revealing residues responsible for binding NADP. Using a combination of structural homology, molecular docking, and quantum chemistry calculations, we have predicted the binding site of CHMS. Key histidine residues in a conserved sequence are identified as crucial for binding the hydroxyl group of CHMS and facilitating dehydrogenation with NADP. Mutating these histidine residues results in a loss of enzyme activity, leading to a proposed model for the enzyme's mechanism. These findings are expected to help guide efforts in protein and metabolic engineering to enhance PDC yields in biological routes to polymer feedstock synthesis.

PubMed: 39222681
DOI: 10.1016/j.jbc.2024.107736

実験手法

X-RAY DIFFRACTION (2.34 Å)