3mph

From Proteopedia

The structure of human diamine oxidase complexed with an inhibitor aminoguanidine

PDB ID 3mph

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Structural highlights

3mph is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.05Å
Ligands:	, , , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

AOC1_HUMAN Catalyzes the degradation of compounds such as putrescine, histamine, spermine, and spermidine, substances involved in allergic and immune responses, cell proliferation, tissue differentiation, tumor formation, and possibly apoptosis. Placental DAO is thought to play a role in the regulation of the female reproductive function.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

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 A resolution shows that the aminoguanidine forms a covalent adduct with the TPQ and that the site is approximately 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.

Correlation of Active Site Metal Content in Human Diamine Oxidase with Trihydroxyphenylalanine Quinone Cofactor Biogenesis .,McGrath AP, Caradoc-Davies T, Collyer CA, Guss JM Biochemistry. 2010 Sep 1. PMID:20722416^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ McGrath AP, Caradoc-Davies T, Collyer CA, Guss JM. Correlation of Active Site Metal Content in Human Diamine Oxidase with Trihydroxyphenylalanine Quinone Cofactor Biogenesis . Biochemistry. 2010 Sep 1. PMID:20722416 doi:10.1021/bi1010915