Linked Life Data

11867636

Source:http://linkedlifedata.com/resource/pubmed/id/11867636

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
18
pubmed:dateCreated
2002-4-29
pubmed:abstractText
Indoleamine 2,3-dioxygenase is a heme enzyme that catalyzes the oxidative degradation of L-Trp and other indoleamines. We have used resonance Raman spectroscopy to characterize the heme environment of purified recombinant human indoleamine 2,3-dioxygenase (hIDO). In the absence of L-Trp, the spectrum of the Fe(3+) form displayed six-coordinate, mixed high and low spin character. Addition of L-Trp triggered a transition to predominantly low spin with two Fe-OH(-) stretching modes identified at 546 and 496 cm(-1), suggesting H-bonding between the NH group of the pyrrole ring of L-Trp and heme-bound OH(-). The distal pocket of Fe(3+) hIDO was explored further by an exogenous heme ligand, CN(-); again, binding of L-Trp introduced strong H-bonding and/or steric interactions to the heme-bound CN(-). On the other hand, the spectrum of Fe(2+) hIDO revealed a five-coordinate and high spin heme with or without L-Trp bound. The proximal Fe-His stretching mode, identified at 236 cm(-1), did not shift upon L-Trp addition, indicating that the proximal Fe-His bond strength is not affected by binding of the substrate. The high Fe-His stretching frequency suggests that Fe(2+) hIDO has a strong "peroxidase-like" Fe-His bond. Using CO as a structural probe for the distal environment of Fe(2+) hIDO revealed that binding of L-Trp in the distal pocket converted IDO to a peroxidase-like enzyme. Binding of L-Trp also caused conformational changes to the heme vinyl groups, which were independent of changes of the spin and coordination state of the heme iron. Together these data indicate that the strong proximal Fe-His bond and the strong H-bonding and/or steric interactions between l-Trp and dioxygen in the distal pocket are likely crucial for the enzymatic activity of hIDO.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
3
pubmed:volume
277
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
15788-94
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
The heme environment of recombinant human indoleamine 2,3-dioxygenase. Structural properties and substrate-ligand interactions.
pubmed:affiliation
Biochemistry Group, The Heart Research Institute, 145 Missenden Road, Camperdown, New South Wales 2050, Australia.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't