PDBsum entry 3hii

Oxidoreductase

PDB id: 3hii

Contents

Protein chains

715 a.a. *

Ligands

NAG-NAG-BMA

NAG-NAG ×5

GOL

PNT ×2

Metals

_CU ×2

_CA ×4

Waters ×916

* Residue conservation analysis

PDB id:

3hii

Name:

Oxidoreductase

Title:

Crystal structure of human diamine oxidase in complex with the inhibitor pentamidine

Structure:

Amiloride-sensitive amine oxidase. Chain: a, b. Synonym: diamine oxidase, dao, amiloride-binding protein, abp, histaminase, kidney amine oxidase, kao. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: abp1. Expressed in: drosophila melanogaster. Expression_system_taxid: 7227. Expression_system_cell_line: schneider 2

Resolution:

2.15Å R-factor: 0.184 R-free: 0.221

Authors:

A.P.Mcgrath,J.M.Guss

Key ref:

A.P.McGrath et al. (2009). Structure and inhibition of human diamine oxidase. Biochemistry, 48, 9810-9822. PubMed id: 19764817

Date:

20-May-09 Release date: 20-Oct-09

Protein chains

P19801  (AOC1_HUMAN) -  Amiloride-sensitive amine oxidase [copper-containing] from Homo sapiens

Seq: 751 a.a.

Struc: 715 a.a.*

* PDB and UniProt seqs differ at 3 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.1.4.3.22 - diamine oxidase.
• Reaction: histamine + O2 + H2O = imidazole-4-acetaldehyde + H2O2 + NH4⁺

histamine + O2 + H2O = imidazole-4-acetaldehyde + H2O2 (Bound ligand (Het Group name = NAG) matches with 46.67% similarity) + NH4(+)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

Biochemistry 48:9810-9822 (2009)

PubMed id: 19764817

Structure and inhibition of human diamine oxidase.

A.P.McGrath, K.M.Hilmer, C.A.Collyer, E.M.Shepard, B.O.Elmore, D.E.Brown, D.M.Dooley, J.M.Guss.

ABSTRACT

Humans have three functioning genes that encode copper-containing amine oxidases. The product of the AOC1 gene is a so-called diamine oxidase (hDAO), named for its substrate preference for diamines, particularly histamine. hDAO has been cloned and expressed in insect cells and the structure of the native enzyme determined by X-ray crystallography to a resolution of 1.8 A. The homodimeric structure has the archetypal amine oxidase fold. Two active sites, one in each subunit, are characterized by the presence of a copper ion and a topaquinone residue formed by the post-translational modification of a tyrosine. Although hDAO shares 37.9% sequence identity with another human copper amine oxidase, semicarbazide sensitive amine oxidase or vascular adhesion protein-1, its substrate binding pocket and entry channel are distinctly different in accord with the different substrate specificities. The structures of two inhibitor complexes of hDAO, berenil and pentamidine, have been refined to resolutions of 2.1 and 2.2 A, respectively. They bind noncovalently in the active-site channel. The inhibitor binding suggests that an aspartic acid residue, conserved in all diamine oxidases but absent from other amine oxidases, is responsible for the diamine specificity by interacting with the second amino group of preferred diamine substrates.