Linked Life Data

17004840

Source:http://linkedlifedata.com/resource/pubmed/id/17004840

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
39
pubmed:dateCreated
2006-9-28
pubmed:abstractText
Dihydroorotate dehydrogenase (DHOD) catalyzes the only redox reaction in the pathway for pyrimidine biosynthesis. In this reaction, a proton is transferred from a carbon atom of the substrate to a serine residue, and a hydride is transferred from another carbon atom of the substrate to a cofactor. The deprotonation of the substrate is postulated to involve a proton relay mechanism along a hydrogen bonding pathway in the active site. In this paper, molecular dynamics simulations are used to identify and characterize potential hydrogen bonding pathways that could facilitate the redox reaction catalyzed by human DHOD. The observed pathways involve hydrogen bonding of the active base serine to a water molecule, which is hydrogen bonded to the substrate carboxylate group or a threonine residue. The threonine residue is positioned to enable proton transfer to another water molecule leading to the bulk solvent. The impact of mutating the active base serine to cysteine is also investigated. This mutation is found to increase the average donor-acceptor distances for proton and hydride transfer and to disrupt the hydrogen bonding pathways observed for the wild-type enzyme. These effects could lead to a significant decrease in enzyme activity, as observed experimentally for the analogous mutant in Escherichia coli DHOD.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1520-6106
pubmed:author
pubmed:issnType
Print
pubmed:day
5
pubmed:volume
110
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
19704-10
pubmed:dateRevised
2007-12-3
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Hydrogen bonding pathways in human dihydroorotate dehydrogenase.
pubmed:affiliation
Department of Chemistry, 104 Chemistry Building, Pennsylvania State University, University Park, 16802, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural