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Exploration of subsite binding specificity of human cathepsin D through kinetics and rule-based molecular modeling by Paula E. Scarborough; Ben M. Dunn; Kunchur Guruprasad; Chris Topham; Tom L. Blundell; Gary R. Richo; Gregory E. Conner is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.

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## Abstract The family of aspartic proteinases includes several human enzymes that may play roles in both physiological and pathophysiological processes. The human lysosomal aspartic proteinase cathepsin D is thought to function in the normal degradation of intracellular and endocytosed proteins but has also emerged as a prognostic indicator of breast tumor invasiveness. Presented here are results from a continuing effort to elucidate the factors that contribute to specificity of ligand binding at individual subsites within the cathepsin D active site. The synthetic peptide Lys‐Pro‐Ile‐Glu‐Phe^\*^Nph‐Arg‐Leu has proven to be an excellent chromogenic substrate for cathepsin D yielding a value of __k~cat~/K~m~__ = 0.92 × 10^−6^ s^−1^ M^−1^ for enzyme isolated from human placenta. In contrast, the peptide Lys‐Pro‐Ala‐Lys‐Phe^\*^Nph‐Arg‐Leu and all derivatives with Ala‐Lys in the P~3~‐P~2~ positions are either not cleaved at all or cleaved with extremely poor efficiency. To explore the binding requirements of the S~3~ and S~2~ subsites of cathepsin D, a series of synthetic peptides was prepared with systematic replacements at the P~2~ position fixing either Ile or Ala in P~3~. Kinetic

Who reads Exploration of subsite binding specificity of human cathepsin D through kinetics and rule-based molecular modeling?

Author

Paula E. Scarborough; Ben M. Dunn; Kunchur Guruprasad; Chris Topham; Tom L. Blundell; Gary R. Richo; Gregory E. Conner

Publisher

Cold Spring Harbor Laboratory Press; Wiley (John Wiley & Sons); Wiley-Blackwell; Wiley (ISSN 0961-8368)

Published

1993

Language

EN

Field

Biochemistry, Genetics and Molecular Biology (Life Sciences)