1vgc
GAMMA-CHYMOTRYPSIN L-PARA-CHLORO-1-ACETAMIDO BORONIC ACID INHIBITOR COMPLEX
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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
1VGC is a Protein complex structure of sequences from Bos taurus with SO4 and V36 as ligands. Active as Chymotrypsin, with EC number 3.4.21.1 Structure known Active Site: CAT. 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
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