Linked Life Data

10550686

Source:http://linkedlifedata.com/resource/pubmed/id/10550686

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
1999-11-30
pubmed:abstractText
Ceruloplasmin is a multi-copper oxidase, which contains most of the copper present in the plasma. It is an acute-phase reactant that exhibits a two- to three-fold increase over the normal concentration of 300 microg/ml in adult plasma. However, the precise physiological role(s) of ceruloplasmin has been the subject of intensive debate and it is likely that the enzyme has a multi-functional role, including iron oxidase activity and the oxidation of biogenic amines. The three-dimensional X-ray structure of the human enzyme was elucidated in 1996 and showed that the molecule was composed of six cupredoxin-type domains arranged in a triangular array. There are six integral copper atoms per molecule (mononuclear sites in domains 2, 4 and 6 and a trinuclear site between domains 1 and 6) and two labile sites with roughly 50% occupancy. Further structural studies on the binding of metal cations by the enzyme indicated a putative mechanism for ferroxidase activity. In this paper we report medium-resolution X-ray studies (3.0-3.5 A) which locate the binding sites for an inhibitor (azide) and various substrates [aromatic diamines, biogenic amines and (+)-lysergic acid diethylamide, LSD]. The binding site of the azide moiety is topologically equivalent to one of the sites reported for ascorbate oxidase. However, there are two distinct binding sites for amine substrates: aromatic diamines bind on the bottom of domain 4 remote from the mononuclear copper site, whereas the biogenic amine series typified by serotonin, epinephrine and dopa bind in close vicinity to that utilised by cations in domain 6 and close to the mononuclear copper. These binding sites are discussed in terms of possible oxidative mechanisms. The binding site for LSD is also reported.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/4-phenylenediamine, http://linkedlifedata.com/resource/pubmed/chemical/Azides, http://linkedlifedata.com/resource/pubmed/chemical/Ceruloplasmin, http://linkedlifedata.com/resource/pubmed/chemical/Dihydroxyphenylalanine, http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Epinephrine, http://linkedlifedata.com/resource/pubmed/chemical/Lysergic Acid Diethylamide, http://linkedlifedata.com/resource/pubmed/chemical/Norepinephrine, http://linkedlifedata.com/resource/pubmed/chemical/Oxidoreductases, http://linkedlifedata.com/resource/pubmed/chemical/Phenylenediamines, http://linkedlifedata.com/resource/pubmed/chemical/Serotonin, http://linkedlifedata.com/resource/pubmed/chemical/copper oxidase
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0949-8257
pubmed:author
pubmed:issnType
Print
pubmed:volume
4
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
579-87
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
An X-ray crystallographic study of the binding sites of the azide inhibitor and organic substrates to ceruloplasmin, a multi-copper oxidase in the plasma.
pubmed:affiliation
CCLRC Daresbury Laboratory, Warrington, Cheshire WA4 4AD, UK.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't