Linked Life Data

19217614

Source:http://linkedlifedata.com/resource/pubmed/id/19217614

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2009-3-24
pubmed:abstractText
Despite decades of its use in diabetes research, the mechanism of cytotoxicity of streptozotocin (STZ) toward pancreatic beta-islet cells has remained a topic of discussion. Although STZ toxicity is likely a function of its capacity to promote DNA alkylation, it has been proposed that STZ induces pancreatic beta-cell death through O-GlcNAcase inhibition. In this report, we explore the binding mode of STZ to a close homolog of human O-GlcNAcase, BtGH84 from Bacteroides thetaiotaomicron. Our results show that STZ binds in the enzyme active site in its intact form, without the formation of a covalent adduct, consistent with solution studies on BtGH84 and human O-GlcNAcase, as well as with structural work on a homolog from Clostridium perfringens. The active site of the BtGH84 is considerably deformed upon STZ binding and as a result the catalytic machinery is expelled from the binding cavity.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1873-426X
pubmed:author
pubmed:issnType
Electronic
pubmed:day
31
pubmed:volume
344
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
627-31
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Structural insight into the mechanism of streptozotocin inhibition of O-GlcNAcase.
pubmed:affiliation
Department of Chemistry, Structural Biology Laboratory, The University of York, Heslington, York, YO10 5YW, UK.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't