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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
16
|
| pubmed:dateCreated |
1993-9-24
|
| pubmed:abstractText |
Electrospray ionization mass spectrometry (ESI-MS) and tandem mass spectrometry (MS/MS) have been used for the first time to study the interaction of human alpha-thrombin with methyl 3-(2-methyl-1-oxopropoxy)[1]benzothieno[3,2-b]furan-2-carbox ylate (LY806303; 1), a potent and selective inhibitor whose mechanism of action was never fully defined. Using ESI-MS, it is shown that inhibitor 1 covalently modifies human alpha-thrombin as evidenced by a shift in the molecular weight of the native protein by 72 Da, which is consistent with isobutyrylation (C4H7O; 71 Da) of the enzyme at a single site. Tryptic digestion of the modified protein and tandem mass spectral analysis of isolated peptide fragments indicate that compound 1 acylates Ser-205 of the heavy chain of alpha-thrombin. Ser-205, along with His-43 and Asp-99 make up the catalytic triad within the active site of thrombin.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Aug
|
| pubmed:issn |
0022-2623
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
6
|
| pubmed:volume |
36
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
2350-5
|
| pubmed:dateRevised |
2006-11-15
|
| pubmed:meshHeading | |
| pubmed:year |
1993
|
| pubmed:articleTitle |
Characterization of the interaction between human alpha-thrombin and methyl 3-(2-methyl-1-oxopropoxy)[1]benzothieno[3,2-b]furan-2-carboxylate (LY806303) using electrospray mass spectrometry and tandem mass spectrometry.
|
| pubmed:affiliation |
Division of Cardiovascular Research, Lilly Research Laboratories, Indianapolis, Indiana 46285.
|
| pubmed:publicationType |
Journal Article
|