Total chemical synthesis of a D-enzyme: the enantiomers of HIV-1 protease show reciprocal chiral substrate specificity [corrected].
The D and L forms of the enzyme HIV-1 protease have been prepared by total chemical synthesis. The two proteins had identical covalent structures. However, the folded protein-enzyme enantiomers showed reciprocal chiral specificity on peptide substrates. That is, each enzyme enantiomer cut only the corresponding substrate enantiomer. Reciprocal chiral specificity was also evident in the effect of enantiomeric inhibitors. These data imply that the folded forms of the chemically synthesized D- and L-enzyme molecules are mirror images of one another in all elements of the three-dimensional structure. Enantiomeric proteins are expected to display reciprocal chiral specificity in all aspects of their biochemical interactions.
Milton
R C
RC
Department of Cell Biology, Scripps Research Institute, La Jolla, CA 92037.
Milton
S C
SC
Kent
S B
SB
D000595:Amino Acid Sequence; D000596:Amino Acids; D016333:HIV Protease / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*; D007700:Kinetics; D046911:Macromolecular Substances; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000494:pharmacology; D011487:Protein Conformation; D013237:Stereoisomerism; D013379:Substrate Specificity; D014961:X-Ray Diffraction
D000596:Amino Acids; D046911:Macromolecular Substances; D009842:Oligopeptides; D016333:HIV Protease