Structural basis for specificity of papain-like cysteine protease proregions toward their cognate enzymes.
Synthetic peptides corresponding to the proregions of papain-like cysteine proteases have been shown to be good and selective inhibitors of their parental enzymes. The molecular basis for their selectivity, quite remarkable in some cases, is not fully understood. The recent determination of the crystal structures of three distinct papain-like cysteine protease zymogens allows detailed structural comparisons to be made. The reasons for the specificity shown by each proregion toward its cognate enzyme are explained in terms of the three-dimensional structure of the proregion and the interface between the mature enzyme and the proregion. These comparisons reveal that insertion and substitution of amino acids within the proregion cause major rearrangement of sidechains on the enzyme/proregion interface, allowing detailed surface and charge recognition.
Groves
M R
MR
Laboratory of Molecular Biophysics, Department of Biochemistry, University of Oxford, United Kingdom.
Coulombe
R
R
Jenkins
J
J
Cygler
M
M
D000595:Amino Acid Sequence; D001665:Binding Sites; D056668:Cathepsin L; D002403:Cathepsins / Q000737:chemistry; D003546:Cysteine Endopeptidases / Q000737:chemistry; D004792:Enzyme Precursors / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010206:Papain / Q000737:chemistry* / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
D004792:Enzyme Precursors; D002403:Cathepsins; D003546:Cysteine Endopeptidases; C103228:procaricain; C063905:procathepsin L; D056668:Cathepsin L; D010206:Papain