1vsb: Difference between revisions
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'''SUBTILISIN CARLSBERG L-PARA-CHLOROPHENYL-1-ACETAMIDO BORONIC ACID INHIBITOR COMPLEX''' | '''SUBTILISIN CARLSBERG L-PARA-CHLOROPHENYL-1-ACETAMIDO BORONIC ACID INHIBITOR COMPLEX''' | ||
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[[Category: Pai, E F.]] | [[Category: Pai, E F.]] | ||
[[Category: Stoll, V S.]] | [[Category: Stoll, V S.]] | ||
[[Category: | [[Category: Boronic acid inhibitor]] | ||
[[Category: | [[Category: Hydrolase]] | ||
[[Category: | [[Category: Serine protease]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 12:51:52 2008'' | |||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | |||
Revision as of 12:51, 3 May 2008
SUBTILISIN CARLSBERG L-PARA-CHLOROPHENYL-1-ACETAMIDO BORONIC ACID INHIBITOR COMPLEX
OverviewOverview
In order to probe the structural basis of stereoselectivity in the serine protease family, a series of enantiomeric boronic acids RCH2CH(NHCOCH3)B(OH)2 has been synthesized and kinetically characterized as transition-state analog inhibitors using alpha-chymotrypsin and subtilisin Carlsberg as model systems. When the R-substituent in this series was changed from a p-chlorophenyl to a 1-naphthyl group, alpha-chymotrypsin, but not subtilisin, reversed its usual preference for l-enantiomers and bound more tightly to the D-enantiomer [Martichonok, V., & Jones, J. B. (1996) J. Am. Chem. Soc. 118, 950-958]. The structural factors responsible for the differences in stereoselectivity between the two enzymes have been explored by X-ray crystallographic examination of subtilisin Carlsberg and gamma-chymotrypsin complexes of the L- and D-enantiomers of p-chlorophenyl and 1-naphthyl boronic acid derivatives. In both enzymes, the L-isomers of the inhibitors, which are more closely related to the natural L-amino acid substrates, form tetrahedral adducts, covalently linking the central boron atom and Ogamma of the catalytic serine. The d-isomers, however, differ in the way they interact with subtilisin or gamma-chymotrypsin. With subtilisin, both the D-p-chlorophenyl and D-1-naphthyl inhibitor complexes form covalent Ser Ogamma-to-boron bonds, but with gamma-chymotrypsin, the same inhibitors lead to novel tetrahedral adducts covalently linking both Ser195 Ogamma and His57 Nepsilon2 covalently via the boron atom.
About this StructureAbout this Structure
1VSB is a Single protein structure of sequence from Bacillus licheniformis. Full crystallographic information is available from OCA.
ReferenceReference
Differences in binding modes of enantiomers of 1-acetamido boronic acid based protease inhibitors: crystal structures of gamma-chymotrypsin and subtilisin Carlsberg complexes., Stoll VS, Eger BT, Hynes RC, Martichonok V, Jones JB, Pai EF, Biochemistry. 1998 Jan 13;37(2):451-62. PMID:9425066 Page seeded by OCA on Sat May 3 12:51:52 2008