Cathepsins

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Ribbon model of Cathepsin K.

Cathepsins (also Kat (h) epsine from Greek καθεψειν - digest) are endoproteases that can be found in lysosomes , eosinophilic granulocytes and osteoclasts , for example , and cause hydrolytic degradation of the extracellular matrix and the basement membrane ( proteases are protein-splitting enzymes ). You are e.g. B. involved in the breakdown of cell organelles , such as overaged mitochondria or collagen-containing bone matrix. The cathepsins are probably also involved in angiogenesis , i.e. the formation of new blood vessels in the course of wound healing and invasive tumor growth .

Cathepsins can be proven to be an unfavorable prognostic marker in various tumors such as pancreatic cancer .

It was discovered by Richard Willstätter and Eugen Baumann in 1929 .

Table of Cathepsins

Gene (HGNC) Gene locus (human) Protein ( UniProt ) MEROPS Enzyme ( EC number ) OMIM Remarks
CTSA 20q13.12 P10619 S10.002 3.4.16.5 256540 Lysosomes ; Galactosialidosis
CTSB 8p23.1 P07858 C01.060 3.4.22.1 116810 Lysosomes
CTSC 11q14.2 P53634 C01.070 3.4.14.1 602365 Lysosomes , especially lungs, kidneys, placenta; Papillon-Lefèvre Syndrome ; Haim-Munk Syndrome ; juvenile periodontal disease
CTSD 11p15.5 P07339 A01.009 3.4.23.5 116840 Lysosomes ; Neural ceroid lipofuscinosis type 10 (NCL10)
CTSE 1q32.1 P14091 A01.010 3.4.23.34 116890 Endosomes , esp. Stomach, Clara cells of the lungs, activated B-lymphocytes
CTSF 11q13.2 Q9UBX1 C01.018 3.4.22.41 603539 Lysosomes , esp. Heart, muscles, brain, genitals, ovaries
CTSG 14q12 P08311 S01.133 3.4.21.20 116830
CTSH 15q25.1 P09668 C01.040 3.4.22.16 116820 Lysosomes
CTSK 1q21 P43235 C01.036 3.4.22.38 601105 Lysosomes ; Pycnodysostosis
CTSL1 9q21.33 P07711 C01.032 3.4.22.15 116880 Lysosomes
CTSL2 9q22.33 O60911 C01.009 3.4.22.43 603308 Lysosomes , esp. Thymus, genitals, cornea
CTSO 4q32.1 P43234 C01.035 3.4.22.42 600550 Ovaries, kidneys, placenta
CTSS 1q21 P25774 C01.034 3.4.22.27 116845 Lysosomes
CTSW 11q13.1 P56202 C01.037 3.4.22.- 602364 Killer cells, T cells
CTSZ 20q13.32 Q9UBR2 C01.013 3.4.18.1 603169 Lysosomes


Inhibitors

Certain peptides cyclized via disulfide bridges have a potentially inhibitory effect on the human cathepsins L, B, H and K.

Individual evidence

  1. Marco Niedergethmann, Birgit Wostbrock, Jörg W. Sturm, Frank Willeke, Stefan Post, Ralf Hildenbrand: Prognostic impact of cysteine ​​proteases cathepsin B and cathepsin L in pancreatic adenocarcinoma. In: Pancreas , Volume 29, No. 3, October 2004, pp. 204-211.
  2. ^ Wolf-Dieter Müller-Jahncke, Chistoph Friedrich, Ulrich Meyer: Medicinal history . 2nd, revised and expanded edition. Wissenschaftliche Verlagsgesellschaft mbH, Stuttgart 2005, ISBN 978-3-8047-2113-5 , p. 114 .
  3. Tomaž Bratkovič, Mojca Lunder, Tatjana Popovič, Samo Kreft, Boris Turk, Borut Štrukelj, Uroš Urleb: Affinity selection to papain yields potent peptide inhibitors of cathepsins L, B, H, and K. In: Biochemical and Biophysical Research Communications , volume 332, No. 3, July 8, 2005, pp. 897-903, doi : 10.1016 / j.bbrc.2005.05.028 .

literature