PDBsum entry 1vsb

Serine protease

PDB id: 1vsb

Contents

Protein chain

274 a.a.

Waters ×84

References listed in PDB file

Key reference

• Title: Differences in binding modes of enantiomers of 1-Acetamido boronic acid based protease inhibitors: crystal structures of gamma-Chymotrypsin and subtilisin carlsberg complexes.
• Authors: V.S.Stoll, B.T.Eger, R.C.Hynes, V.Martichonok, J.B.Jones, E.F.Pai.
• Ref.: Biochemistry, 1998, 37, 451-462. [DOI no: 10.1021/bi971166o]
• PubMed id: 9425066

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.

Secondary reference #1

• Title: Probing the specificity of the serine proteases subtilisin carlsberg and a-Chymotrypsin with enantiomeric 1-Acetamido boronic acids. An unexpected reversal of the normal "l"-Stereoselectivity preference
• Authors: V.Martichonok, J.B.Jones.
• Ref.: j am chem soc, 1996, 118, 950.

Secondary reference #2

• Title: Probing the specificity of the s1 binding site of subtilisin carlsberg with boronic acids.
• Authors: P.Seufer-Wasserthal, V.Martichonok, T.H.Keller, B.Chin, R.Martin, J.B.Jones.
• Ref.: Bioorg Med Chem Lett, 1994, 2, 35-48.
• PubMed id: 7922119

Secondary reference #3

• Title: Enzyme crystal structure in a neat organic solvent.
• Authors: P.A.Fitzpatrick, A.C.Steinmetz, D.Ringe, A.M.Klibanov.
• Ref.: Proc Natl Acad Sci U S A, 1993, 90, 8653-8657. [DOI no: 10.1073/pnas.90.18.8653]
• PubMed id: 8378343

Secondary reference #4

• Title: The structure of subtilopeptidase a. I. X-Ray crystallographic data.
• Authors: G.A.Petsko, D.Tsernoglou.
• Ref.: J Mol Biol, 1976, 106, 453-456.
• PubMed id: 978729