3MPH

The structure of human diamine oxidase complexed with an inhibitor aminoguanidine

3MPH の概要

• エントリーDOI: 10.2210/pdb3mph/pdb
• 関連するPDBエントリー: 3HI7 3HIG 3HII 3K5T
• 分子名称: Amiloride-sensitive amine oxidase, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• 機能のキーワード: oxidoreductase, copper amine oxidase, cao, topaquinone, tpq, diamine oxidase, dao, human, aminoguanidine
• 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: 170035.68

構造登録者

McGrath, A.P.,Guss, J.M. (登録日: 2010-04-27, 公開日: 2010-09-08, 最終更新日: 2023-11-01)

主引用文献

McGrath, A.P.,Caradoc-Davies, T.,Collyer, C.A.,Guss, J.M.
Correlation of active site metal content in human diamine oxidase with trihydroxyphenylalanine quinone cofactor biogenesis
Biochemistry, 49:8316-8324, 2010

PubMed Abstract: Copper-containing amine oxidases (CAOs) require a protein-derived topaquinone cofactor (TPQ) for activity. TPQ biogenesis is a self-processing reaction requiring the presence of copper and molecular oxygen. Recombinant human diamine oxidase (hDAO) was heterologously expressed in Drosophila S2 cells, and analysis indicates that the purified hDAO contains substoichiometric amounts of copper and TPQ. The crystal structure of a complex of an inhibitor, aminoguanidine, and hDAO at 2.05 Å resolution shows that the aminoguanidine forms a covalent adduct with the TPQ and that the site is ∼75% occupied. Aminoguanidine is a potent inhibitor of hDAO with an IC(50) of 153 ± 9 nM. The structure indicates that the catalytic metal site, normally occupied by copper, is fully occupied. X-ray diffraction data recorded below the copper edge, between the copper and zinc edges, and above the zinc edge have been used to show that the metal site is occupied approximately 75% by copper and 25% by zinc and the formation of the TPQ cofactor is correlated with copper occupancy.

PubMed: 20722416
DOI: 10.1021/bi1010915

実験手法

X-RAY DIFFRACTION (2.05 Å)