3VSB

SUBTILISIN CARLSBERG D-NAPHTHYL-1-ACETAMIDO BORONIC ACID INHIBITOR COMPLEX

3VSB の概要

• エントリーDOI: 10.2210/pdb3vsb/pdb
• 分子名称: SUBTILISIN CARLSBERG, TYPE VIII, SODIUM ION (3 entities in total)
• 機能のキーワード: serine protease, hydrolase, boronic acid inhibitors
• 由来する生物種: Bacillus licheniformis
• 細胞内の位置: Secreted: P00780
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 27608.26

構造登録者

Stoll, V.S.,Eger, B.T.,Hynes, R.C.,Martichonok, V.,Jones, J.B.,Pai, E.F. (登録日: 1997-09-25, 公開日: 1998-03-25, 最終更新日: 2023-08-09)

主引用文献

Stoll, V.S.,Eger, B.T.,Hynes, R.C.,Martichonok, V.,Jones, J.B.,Pai, E.F.
Differences in binding modes of enantiomers of 1-acetamido boronic acid based protease inhibitors: crystal structures of gamma-chymotrypsin and subtilisin Carlsberg complexes.
Biochemistry, 37:451-462, 1998

PubMed Abstract: 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.

PubMed: 9425066
DOI: 10.1021/bi971166o

実験手法

X-RAY DIFFRACTION (2.6 Å)