Linked Life Data

19643161

Source:http://linkedlifedata.com/resource/pubmed/id/19643161

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2010-2-1
pubmed:abstractText
Corticosteroid-binding globulin (CBG), a non-inhibitory member of the serine proteinase inhibitor (serpin) super-family, is the high-affinity transport protein for glucocorticoids in vertebrate blood. Plasma CBG is a glycoprotein with 30% of its mass represented by N-linked oligosaccharide chains. Its well-characterized steroid-binding properties represent a "bench-mark data set" used extensively for in silico studies of protein-ligand interactions and drug design. Recent crystal structure analyses of intact rat CBG and cleaved human CBG have revealed the precise topography of the steroid-binding site, and shown that cortisol-bound CBG displays a typical stressed (S) serpin conformation with the reactive center loop (RCL) fully exposed from the central beta-sheet A, while proteolytic cleavage of the RCL results in CBG adopting a relaxed (R) conformation with the cleaved RCL fully inserted within the protein core. These crystal structures have set the stage for mechanistic studies of CBG function which have so far shown that helix D plays a key role in coupling RCL movement and steroid-binding site integrity, and provided evidence for an allosteric mechanism that modulates steroid binding and release from CBG. These studies have also revealed how the irreversible release of steroids occurs after proteolysis and re-orientation of the RCL within the R conformation. This recent insight into the structure and function of CBG reveals how naturally occurring genetic CBG mutations affect steroid binding, and helps understand how proteolysis of CBG enhances the targeted delivery of biologically active steroids to their sites of action.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1872-8057
pubmed:author
pubmed:copyrightInfo
2009 Elsevier Ireland Ltd. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
5
pubmed:volume
316
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3-12
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Molecular and structural basis of steroid hormone binding and release from corticosteroid-binding globulin.
pubmed:affiliation
State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China. linhy@ioz.ac.cn
pubmed:publicationType
Journal Article, Review, Research Support, Non-U.S. Gov't