Active center differences between cathepsins L and B: the S1 binding region.
The substrate peptide bond cleaved by cathepsins B and L is determined not by the amino acid contributing the carboxyl group to this bond as in the case of serine proteases but rather by the presence of a neighboring amino acid with a large hydrophobic side chain. From a study of the inhibitory potency in a series, Cbz-Phe-X-CHN2, in which Phe promotes binding at S2 (terminology of [(1968) Biochem. Biophys. Res. Commun. 32, 898-902]) while the amino acid X probes S1, it is shown that this region of cathepsin L also has the ability to accommodate large hydrophobic side chains. In this respect cathepsin L differs from cathepsin B. Thus Cbz-Phe-Tyr(O-t-Bu)CHN2 inactivates cathepsin L with a rate 2.5 x 10(4) greater than that for cathepsin B.
Kirschke
H
H
Physiologisch-Chemisches Institut der Martin-Luther-Universität, Halle-Wittenberg, Saale, GDR.
Wikstrom
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P
Shaw
E
E
D000596:Amino Acids / Q000502:physiology; D000818:Animals; D001665:Binding Sites; D002401:Cathepsin B / Q000037:antagonists & inhibitors; D056668:Cathepsin L; D002403:Cathepsins / Q000037:antagonists & inhibitors; D003546:Cysteine Endopeptidases; D010450:Endopeptidases; D007202:Indicators and Reagents; D008099:Liver / Q000201:enzymology; D051381:Rats
D000596:Amino Acids; D007202:Indicators and Reagents; D002403:Cathepsins; D010450:Endopeptidases; D003546:Cysteine Endopeptidases; D002401:Cathepsin B; D056668:Cathepsin L; C534280:Ctsl protein, rat