Linked Life Data

19159616

Source:http://linkedlifedata.com/resource/pubmed/id/19159616

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2009-2-6
pubmed:abstractText
PSA (kallikrein hK3) proteolytic activity proved highly sensitive to reducing agents like dithiothreitol (DTT) and dihydrolipoic acid while beta-mercaptoethanol and glutathione were less effective. Ascorbate exhibited no significant inhibitory potential. Loss of activity by reduction could be readily reversed by re-oxidation. Inactivation was associated with the reduction of two out of five conserved disulfides. Mass spectrometry of differentially modified cysteines, and Edman degradation analyses identified Cys 22-Cys 157 and Cys 191-Cys 220 as DDT-sensitive. The highly homologous porcine pancreatic kallikrein (pK1) showed a completely different response: Even at 20 mM DDT, no inactivation was seen; and in this case, only one of the five disulfides (Cys 22-Cys 157) was opened. This indicated that it is the accessabilty of the Cys 191-Cys 220 disulfide near the catalytic serine 195 that decides on the ability of reductants to inactivate the proteolytic activity of PSA. A structural basis for this interpretation is provided when the two homologous proteins were compared with respect to the threedimensional architecture around the crucial disulfide Cys 191-Cys 220 where in the case of PK1, but not in PSA, the phenylalanine-residue (Phe 149) is in an interfering position.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1090-2104
pubmed:author
pubmed:issnType
Electronic
pubmed:day
20
pubmed:volume
379
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1101-6
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Prostate specific antigen: one out of five disulfide bridges determines inactivation by reduction.
pubmed:affiliation
Institut für Biochemie und Molekularbiologie I, Universitätsklinikum Hamburg-Eppendorf, D-20246 Hamburg, Germany. weber@uke.uni-hamburg.de
pubmed:publicationType
Journal Article