3MPH

The structure of human diamine oxidase complexed with an inhibitor aminoguanidine

Summary for 3MPH

• Entry DOI: 10.2210/pdb3mph/pdb
• Related: 3HI7 3HIG 3HII 3K5T
• Descriptor: 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)
• Functional Keywords: oxidoreductase, copper amine oxidase, cao, topaquinone, tpq, diamine oxidase, dao, human, aminoguanidine
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 170035.68

Authors

McGrath, A.P.,Guss, J.M. (deposition date: 2010-04-27, release date: 2010-09-08, Last modification date: 2023-11-01)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.05 Å)