Linked Life Data

15642265

Source:http://linkedlifedata.com/resource/pubmed/id/15642265

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2005-1-11
pubmed:databankReference
pubmed:abstractText
Rho is a hexameric RNA/DNA helicase/translocase that terminates transcription of select genes in bacteria. The naturally occurring antibiotic, bicyclomycin (BCM), acts as a noncompetitive inhibitor of ATP turnover to disrupt this process. We have determined three independent X-ray crystal structures of Rho complexed with BCM and two semisynthetic derivatives, 5a-(3-formylphenylsulfanyl)-dihydrobicyclomycin (FPDB) and 5a-formylbicyclomycin (FB) to 3.15, 3.05, and 3.15 A resolution, respectively. The structures show that BCM and its derivatives are nonnucleotide inhibitors that interact with Rho at a pocket adjacent to the ATP and RNA binding sites in the C-terminal half of the protein. BCM association prevents ATP turnover by an unexpected mechanism, occluding the binding of the nucleophilic water molecule required for ATP hydrolysis. Our data explain why only certain elements of BCM have been amenable to modification and serve as a template for the design of new inhibitors.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0969-2126
pubmed:author
pubmed:issnType
Print
pubmed:volume
13
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
99-109
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Structural mechanism of inhibition of the Rho transcription termination factor by the antibiotic bicyclomycin.
pubmed:affiliation
Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't