Linked Life Data

19117080

Source:http://linkedlifedata.com/resource/pubmed/id/19117080

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
52
pubmed:dateCreated
2008-12-30
pubmed:databankReference
pubmed:abstractText
First identified on the surface of lymphoids as a type II transmembrane protein, CD38 has now been established to have dual functions not only as a receptor but also as a multifunctional enzyme,catalyzing the synthesis of and hydrolysis of a general calcium messenger molecule, cyclic ADP-ribose(cADPR). The receptorial functions of CD38 include the induction of cell adhesion, differentiation,apoptosis, and cytokine production upon antibody ligation. Here we determined the crystal structure of calcium-loaded human CD38 at 1.45 A resolution which reveals that CD38 undergoes dramatic structural changes to an inhibited conformation in the presence of calcium. The structural changes are highly localized and occur in only two regions. The first region is part of the active site and consists of residues 121-141.In the presence of calcium, W125 moves 5 A into the active site and forms hydrophobic interactions with W189. The movement closes the active site pocket and reduces entry of substrates, resulting in inhibition of the enzymatic activity. The structural role of calcium in inducing these conformational changes is readily visualized in the crystal structure. The other region that undergoes calcium-induced changes is at the receptor region, where a highly ordered helix is unraveled to a random coil. The results suggest a novel conformational coupling mechanism, whereby protein interaction targeted at the receptor region can effectively regulate the enzymatic activity of CD38.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1520-4995
pubmed:author
pubmed:issnType
Electronic
pubmed:day
30
pubmed:volume
47
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
13966-73
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Conformational Closure of the Catalytic Site of Human CD38 Induced by Calcium.
pubmed:affiliation
MacCHESS, Cornell High Energy Synchrotron Source, and School of Applied and Engineering Physics, Cornell University, Ithaca, New York 14853, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural