Linked Life Data

10079069

Source:http://linkedlifedata.com/resource/pubmed/id/10079069

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
1999-4-15
pubmed:databankReference
pubmed:abstractText
D-Dopachrome tautomerase shares a low homologous amino acid sequence (33% homology) with the macrophage migration inhibitory factor (MIF) and possesses similar tautomerase activity as well. MIF is a cytokine involved in inflammatory reactions and immune responses. Whereas recent studies have identified MIF as a pituitary hormone and immunoregulator, much less is known about the structural basis of these physiological functions and the real significance of tautomerase activity. Therefore, interest in the structure-function relationship between D-dopachrome tautomerase and MIF has increased, especially with regard to inflammation and immune responses. We have determined the X-ray crystal structure of human D-dopachrome tautomerase at 1.54 A resolution. D-Dopachrome tautomerase folds to form a homotrimer that has extensive contact between subunits by intersubunit beta-sheets. Its overall topology and trimeric formations are similar to those of human MIF. The N-terminal proline is located at the bottom of a positively charged pocket in which the conformations of Lys32 and Ser63 are highly conserved. These positively charged properties are also seen in the active site pocket of human MIF, bacterial 5-(carboxymethyl)-2-hydroxymuconate isomerase (CHMI), and 4-oxalocrotonate tautomerase (4-OT). A detailed comparison of these structures revealed significant differences in the environment around the potential active site, the intersubunit contacts, and charge distribution on the molecular surface. It can be concluded that these features are related to the physiological role and tautomerase activity of MIF and D-dopachrome tautomerase. The present structural study could be helpful for designing effective inhibitors that modulate immunoregulatory and hormone-like effects.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0006-2960
pubmed:author
pubmed:issnType
Print
pubmed:day
16
pubmed:volume
38
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3268-79
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:10079069-Amino Acid Sequence, pubmed-meshheading:10079069-Animals, pubmed-meshheading:10079069-Binding Sites, pubmed-meshheading:10079069-Carbon-Carbon Double Bond Isomerases, pubmed-meshheading:10079069-Cattle, pubmed-meshheading:10079069-Computer Simulation, pubmed-meshheading:10079069-Crystallization, pubmed-meshheading:10079069-Crystallography, X-Ray, pubmed-meshheading:10079069-Humans, pubmed-meshheading:10079069-Intramolecular Oxidoreductases, pubmed-meshheading:10079069-Isomerases, pubmed-meshheading:10079069-Macrophage Migration-Inhibitory Factors, pubmed-meshheading:10079069-Mice, pubmed-meshheading:10079069-Models, Molecular, pubmed-meshheading:10079069-Molecular Sequence Data, pubmed-meshheading:10079069-Protein Structure, Secondary, pubmed-meshheading:10079069-Rats, pubmed-meshheading:10079069-Sequence Homology, Amino Acid
pubmed:year
1999
pubmed:articleTitle
Crystal structure of human D-dopachrome tautomerase, a homologue of macrophage migration inhibitory factor, at 1.54 A resolution.
pubmed:affiliation
Division of Biological Sciences, Graduate School of Science, Hokkaido University, Sapporo, Japan.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't