Proteolityczny kombinat i jego regulatory

• Autorzy: Stój J. , Karpowicz P.

Warianty tytułu

EN

The proteolytic machinery and its regulators

• Języki publikacji: PL

Abstrakty

EN

One of the proteolytic pathways existing in a cell is ubiquitin- proteasome system (UPS). This highly organized and ATP-dependent system is based on the multifunctional enzyme – the proteasome. Ubiquitin in this pathway plays a role of a tag which marks proteins intended for destruction. Ubiquitylated proteins are recognized and degraded by the 26S proteasome. It consists of a cylindrical-shaped proteolytic core – the proteasome 20S, and attached to it regulatory particles 19S (Fig. 2). The core is composed of four rings, each of them formed by seven subunits. The inner â-rings harbour active sites (in Eukaryota two of each kind: chymotrypsin-like (ChT-L), trypsin-like (T-L) and peptidylglutamyl (PGPH)). The outer, á-rings create a gated channel leading to the catalytic chamber [8]. In a latent proteasome the gate is closed by tightly packed N-terminal residues of á subunits (Fig. 4). Due to such architecture the active sites of the proteasome are not freely available for the substrates. An opening of the gate in physiological conditions occurs after binding the activators such as 11S, 19S or PA200. By catalysing degradation of proteins, the UPS is deeply involved in regulation of cellular physiology. It is also involved in removing of misfolded or damaged proteins and supports the immune system by generating antigenic peptides. Defects in functioning of this proteolytic system play a causal role in the development of a number of diseases, including inflammation, neurodegenerative diseases and various cancers [2–6] what is the reason why the proteasome has become an important therapeutic target. Detailed information about the structure, catalytic activities and mechanisms of functioning of the different proteasome complexes existing in cells is essential to understand their role in organisms as well as to develop new compounds which may find pharmaceutical application.

Słowa kluczowe

PL

proteasom; system ubikwityno-proteasomalny; inhibitor; allosteryczność

EN

proteasome; ubiquitin-proteasome system; inhibitor; allostery

• Wydawca: Polskie Towarzystwo Chemiczne
• Czasopismo: Wiadomości Chemiczne
• Rocznik: 2012
• Tom: [Z] 66, 11-12
• Strony: 1097--1118
• Opis fizyczny: Bibliogr. 47 poz., rys., tab.

Twórcy

autor

Stój J.

autor

Karpowicz P.

• Katedra Chemii Medycznej, Wydział Chemii, Uniwersytet Gdański ul. Sobieskiego 18, 80-952 Gdańsk,

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