Linked Life Data

9895279

Source:http://linkedlifedata.com/resource/pubmed/id/9895279

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
1999-3-30
pubmed:abstractText
The bisphosphonates (general structure PO3-R-PO3) competitively inhibit soluble and membrane-bound inorganic pyrophosphatases (PPases) with differing degrees of specificity. Aminomethylenebisphosphonate (AMBP; HC(PO3)2NH2) is a potent, specific inhibitor of the PPase of higher plant vacuoles (V-PPase). To explore the possibility of constructing photoactivatable probes from bisphosphonates to label the active site of V-PPase we analysed the effects of different analogues on the hydrolytic and proton pumping activity of the enzyme. Bisphosphonates with a range of structures inhibited competitively and the effects on PPi hydrolysis correlated with the effects on proton pumping. Low-molecular-mass bisphosphonates containing hydrophilic groups (alpha-NH2 or OH) were the most effective, suggesting that the catalytic site is in a restricted polar pocket. Bisphosphonates containing a benzene ring were less active but the introduction of a nitrogen atom into the ring increased activity. Compounds of the general formula NH2(CH2)nC(PO3)2OH were more inhibitory than compounds of the H(CH2)nC(PO3)2NH2, NH2(CH2)nC(PO3)2NH2 or OH(CH2)nC(PO3)2NH2 series, with activity decreasing as n increased. A nitrogen atom in the carbon chain increased activity but activity was decreased by the presence of an oxygen atom. An analogue with a ring attached via a four-carbon chain, which included an amide linkage and a hydroxy group on the alpha-carbon atom, inhibited competitively (Ki=62.0 microM), suggesting that it may be possible to design bisphosphonate inhibitors which contain a photoactivatable azido group for photoaffinity labelling of V-PPase active site.
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/9895279-1311852, http://linkedlifedata.com/resource/pubmed/commentcorrection/9895279-1400282, http://linkedlifedata.com/resource/pubmed/commentcorrection/9895279-1662506, http://linkedlifedata.com/resource/pubmed/commentcorrection/9895279-16653052, http://linkedlifedata.com/resource/pubmed/commentcorrection/9895279-16653186, http://linkedlifedata.com/resource/pubmed/commentcorrection/9895279-2630251, http://linkedlifedata.com/resource/pubmed/commentcorrection/9895279-2848451, http://linkedlifedata.com/resource/pubmed/commentcorrection/9895279-3504722, http://linkedlifedata.com/resource/pubmed/commentcorrection/9895279-5803538, http://linkedlifedata.com/resource/pubmed/commentcorrection/9895279-7870050, http://linkedlifedata.com/resource/pubmed/commentcorrection/9895279-7942149, http://linkedlifedata.com/resource/pubmed/commentcorrection/9895279-7972521, http://linkedlifedata.com/resource/pubmed/commentcorrection/9895279-8016125, http://linkedlifedata.com/resource/pubmed/commentcorrection/9895279-8223618, http://linkedlifedata.com/resource/pubmed/commentcorrection/9895279-8382487, http://linkedlifedata.com/resource/pubmed/commentcorrection/9895279-8843945, http://linkedlifedata.com/resource/pubmed/commentcorrection/9895279-9286751, http://linkedlifedata.com/resource/pubmed/commentcorrection/9895279-9489011
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0264-6021
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
337 ( Pt 3)
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
373-7
pubmed:dateRevised
2010-9-13
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Structural aspects of the effectiveness of bisphosphonates as competitive inhibitors of the plant vacuolar proton-pumping pyrophosphatase.
pubmed:affiliation
Biochemistry and Physiology Department, IACR-Rothamsted, Harpenden, Hertfordshire AL5 2JQ, U.K. ruth.gordon-weeks@bbsrc.ac.uk
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't