Role of the occluding loop in cathepsin B activity.

The Journal of Biological Chemistry
C IllyJ S Mort

Abstract

Within the lysosomal cysteine protease family, cathepsin B is unique due to its ability to act both as an endopeptidase and a peptidyldipeptidase. This latter capacity to remove C-terminal dipeptides has been attributed to the presence of a 20-residue insertion, termed the occluding loop, that blocks the primed terminus of the active site cleft. Variants of human procathepsin B, where all or part of this element was deleted, were expressed in the yeast Pichia pastoris. A mutant, where the 12 central residues of the occluding loop were deleted, autoprocessed, albeit more slowly than the wild type proenzyme, to yield a mature form of the enzyme with endopeptidase activity comparable with the wild-type cathepsin B, but totally lacking exopeptidase activity. This deletion mutant showed a 40-fold higher affinity for the inhibitor cystatin C, suggesting that the occluding loop normally restricts access of this inhibitor to the active site. In addition, the binding affinity of the cathepsin B propeptide, which is a potent inhibitor of this enzyme, was 50-fold increased, consistent with the finding that the loop reorients on activation of the proenzyme. These results suggest that the endopeptidase activity of cathepsin B is an evolutio...Continue Reading

References

Dec 22, 1992·Biochemistry·T FoxA C Storer
Dec 1, 1990·Trends in Biochemical Sciences·R J Leatherbarrow
Apr 20, 1967·Biochemical and Biophysical Research Communications·I Schechter, A Berger
Oct 25, 1984·Journal of Molecular Biology·I G KamphuisJ Drenth
May 1, 1981·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·J S MortR S Decker
Jan 1, 1981·Methods in Enzymology·A J Barrett, H Kirschke
Feb 17, 1995·Journal of Molecular Biology·P J Berti, A C Storer
Jul 1, 1996·Acta Crystallographica. Section D, Biological Crystallography·J SivaramanM Cygler

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Citations

Oct 7, 1998·Protein Science : a Publication of the Protein Society·P M SteedA K Knap
Dec 21, 2006·Folia Microbiologica·A PavlovaC Gonzalez-Rey
Apr 7, 2006·Parasitology Research·Kelly N DuBoisJames H McKerrow
Dec 17, 2009·Apoptosis : an International Journal on Programmed Cell Death·Volker HeusslerRebecca Stanway
May 2, 2013·Developmental and Comparative Immunology·Donghong NiuJiale Li
Oct 24, 2002·Bioorganic Chemistry·Brian E CathersRobert M Rydzewski
Feb 19, 2002·Molecular and Biochemical Parasitology·M Sajid, J H McKerrow
Mar 10, 2000·Biochimica Et Biophysica Acta·B TurkV Turk
Jan 21, 2000·FEMS Microbiology Reviews·J L Cereghino, J M Cregg
Apr 2, 1998·Current Opinion in Immunology·H A Chapman
Feb 19, 2000·Current Opinion in Immunology·R J Riese, H A Chapman
Apr 3, 2003·Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology·Hitoshi AokiShugo Watabe
Sep 30, 2000·European Journal of Biochemistry·J GuayJ A Mancini
Jan 6, 2010·The Journal of Biological Chemistry·Ji-Eun AhnKeyan Zhu-Salzman
Aug 13, 2011·The Journal of Biological Chemistry·Adéla JílkováMichael Mareš
Mar 23, 2002·Protein Science : a Publication of the Protein Society·John W CrabbHenry F Hoff
Dec 7, 2011·Antimicrobial Agents and Chemotherapy·Marie SchaefferGraham H Coombs
Feb 5, 2000·American Journal of Respiratory Cell and Molecular Biology·P J WoltersG H Caughey
May 17, 2008·PLoS Pathogens·Naotoshi TsujiKozo Fujisaki
Jan 12, 2001·Biological Chemistry·T KatoK Okuda
Feb 7, 2008·Journal of Periodontology·Taichi ItoTetsuo Kato
Aug 10, 2000·Analytical Biochemistry·J C Krupa, J S Mort

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