Linked Life Data

12069585

Source:http://linkedlifedata.com/resource/pubmed/id/12069585

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
25
pubmed:dateCreated
2002-6-18
pubmed:databankReference
pubmed:abstractText
The crystal structures of the copper-dependent Aspergillus japonicus quercetin 2,3-dioxygenase (2,3QD) complexed with the inhibitors diethyldithiocarbamate (DDC) and kojic acid (KOJ) are reported at 1.70 and 2.15 A resolution, respectively. Both inhibitors asymmetrically chelate the metal center and assume a common orientation in the active site cleft. Their molecular plane blocks access to the inner portion of the cavity which is lined by the side chains of residues Met51, Thr53, Phe75, Phe114, and Met123 and which is believed to bind the flavonol B-ring of the natural substrate. The binding of the inhibitors brings order into the mixed coordination observed in the native enzyme. DDC and KOJ induce a single conformation of the Glu73 side chain, although in different ways. In the presence of DDC, Glu73 is detached from the copper ion with its carboxylate moiety pointing away from the active site cavity. In contrast, when KOJ is bound, Glu73 ligates the Cu ion through its O(epsilon)(1) atom with a monodentate geometry. Compared to the native coordinating conformation, this conformation is approximately 90 degrees rotated about the chi(3) angle. This latter Glu73 conformation is compatible with the presence of a bound substrate.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0006-2960
pubmed:author
pubmed:issnType
Print
pubmed:day
25
pubmed:volume
41
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
7955-62
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Functional analysis of the copper-dependent quercetin 2,3-dioxygenase. 1. Ligand-induced coordination changes probed by X-ray crystallography: inhibition, ordering effect, and mechanistic insights.
pubmed:affiliation
Laboratory of Biophysical Chemistry, Department of Chemistry, University of Groningen, Nijenborgh 4, 9747 AG Groningen, The Netherlands.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't