7RM9

Human Malate Dehydrogenase I (MDHI)

7RM9 の概要

• エントリーDOI: 10.2210/pdb7rm9/pdb
• 分子名称: Malate dehydrogenase, cytoplasmic, MALONATE ION (3 entities in total)
• 機能のキーワード: oxidoreductase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 73044.17

構造登録者

McCue, W.,Finzel, B.C. (登録日: 2021-07-27, 公開日: 2022-01-05, 最終更新日: 2023-10-18)

主引用文献

McCue, W.M.,Finzel, B.C.
Structural Characterization of the Human Cytosolic Malate Dehydrogenase I.
Acs Omega, 7:207-214, 2022

PubMed Abstract: The first crystal structure of the human cytosolic malate dehydrogenase I (MDH1) is described. Structure determination at a high resolution (1.65 Å) followed production, isolation, and purification of human MDH1 using a bacterial expression system. The structure is a binary complex of MDH1 with only a bound malonate molecule in the substrate binding site. Comparisons of this structure with malate dehydrogenase enzymes from other species confirm that the human enzyme adopts similar secondary, tertiary, and quaternary structures and that the enzyme retains a similar conformation even when nicotinamide adenine dinucleotide (NAD) is not bound. A comparison to the highly homologous porcine () MDH1 ternary structures leads to the conclusion that only small conformational differences are needed to accommodate binding by NAD or other NAD mimetics. Conformational differences observed in the second subunit show that the NAD binding elements are nevertheless quite flexible. Comparison of MDH1 to the human mitochondrial malate dehydrogenase (MDH2) reveals some key differences in the α7-α8 loop, which lies directly beneath the substrate binding pocket. These differences might be exploited in the structure-assisted design of selective small molecule inhibitors of MDH1, an emerging target for the development of anticancer therapeutics.

PubMed: 35036692
DOI: 10.1021/acsomega.1c04385

実験手法

X-RAY DIFFRACTION (1.65 Å)