Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
14
pubmed:dateCreated
2008-8-8
pubmed:abstractText
Among bacterial topoisomerase I enzymes, a conserved methionine residue is found at the active site next to the nucleophilic tyrosine. Substitution of this methionine residue with arginine in recombinant Yersinia pestis topoisomerase I (YTOP) was the only substitution at this position found to induce the SOS response in Escherichia coli. Overexpression of the M326R mutant YTOP resulted in approximately 4 log loss of viability. Biochemical analysis of purified Y. pestis and E. coli mutant topoisomerase I showed that the Met to Arg substitution affected the DNA religation step of the catalytic cycle. The introduction of an additional positive charge into the active site region of the mutant E. coli topoisomerase I activity shifted the pH for optimal activity and decreased the Mg(2+) binding affinity. This study demonstrated that a substitution outside the TOPRIM motif, which binds Mg(2+)directly, can nonetheless inhibit Mg(2+) binding and DNA religation by the enzyme, increasing the accumulation of covalent cleavage complex, with bactericidal consequence. Small molecules that can inhibit Mg(2+) dependent religation by bacterial topoisomerase I specifically could be developed into useful new antibacterial compounds. This approach would be similar to the inhibition of divalent ion dependent strand transfer by HIV integrase in antiviral therapy.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/18653534-10681504, http://linkedlifedata.com/resource/pubmed/commentcorrection/18653534-11395412, http://linkedlifedata.com/resource/pubmed/commentcorrection/18653534-11809772, http://linkedlifedata.com/resource/pubmed/commentcorrection/18653534-12042765, http://linkedlifedata.com/resource/pubmed/commentcorrection/18653534-12570763, http://linkedlifedata.com/resource/pubmed/commentcorrection/18653534-12844870, http://linkedlifedata.com/resource/pubmed/commentcorrection/18653534-12844883, http://linkedlifedata.com/resource/pubmed/commentcorrection/18653534-1328167, http://linkedlifedata.com/resource/pubmed/commentcorrection/18653534-15115398, http://linkedlifedata.com/resource/pubmed/commentcorrection/18653534-15139806, http://linkedlifedata.com/resource/pubmed/commentcorrection/18653534-15215234, http://linkedlifedata.com/resource/pubmed/commentcorrection/18653534-16159875, http://linkedlifedata.com/resource/pubmed/commentcorrection/18653534-16285921, http://linkedlifedata.com/resource/pubmed/commentcorrection/18653534-16291214, http://linkedlifedata.com/resource/pubmed/commentcorrection/18653534-16350949, http://linkedlifedata.com/resource/pubmed/commentcorrection/18653534-16357859, http://linkedlifedata.com/resource/pubmed/commentcorrection/18653534-16418335, http://linkedlifedata.com/resource/pubmed/commentcorrection/18653534-16464437, http://linkedlifedata.com/resource/pubmed/commentcorrection/18653534-16582104, http://linkedlifedata.com/resource/pubmed/commentcorrection/18653534-16990856, http://linkedlifedata.com/resource/pubmed/commentcorrection/18653534-17005407, http://linkedlifedata.com/resource/pubmed/commentcorrection/18653534-17293019, http://linkedlifedata.com/resource/pubmed/commentcorrection/18653534-17317696, http://linkedlifedata.com/resource/pubmed/commentcorrection/18653534-17342143, http://linkedlifedata.com/resource/pubmed/commentcorrection/18653534-17346206, http://linkedlifedata.com/resource/pubmed/commentcorrection/18653534-18096618, http://linkedlifedata.com/resource/pubmed/commentcorrection/18653534-18174972, http://linkedlifedata.com/resource/pubmed/commentcorrection/18653534-18310346, http://linkedlifedata.com/resource/pubmed/commentcorrection/18653534-1908806, http://linkedlifedata.com/resource/pubmed/commentcorrection/18653534-2549853, http://linkedlifedata.com/resource/pubmed/commentcorrection/18653534-3015947, http://linkedlifedata.com/resource/pubmed/commentcorrection/18653534-338610, http://linkedlifedata.com/resource/pubmed/commentcorrection/18653534-9477115, http://linkedlifedata.com/resource/pubmed/commentcorrection/18653534-9504803, http://linkedlifedata.com/resource/pubmed/commentcorrection/18653534-9722641, http://linkedlifedata.com/resource/pubmed/commentcorrection/18653534-9857042
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1362-4962
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
36
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4788-96
pubmed:dateRevised
2010-12-3
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Inhibition of Mg2+ binding and DNA religation by bacterial topoisomerase I via introduction of an additional positive charge into the active site region.
pubmed:affiliation
Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, New York 10595, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural