Page 185 - Color Atlas of Biochemistry
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176 Metabolism
Proteolysis molecules) are marked by covalent linkage
with chains of the small protein ubiquitin.
The ubiquitin is previously activated by the
A. Proteolytic enzymes
introduction of reactive thioester groups.
Combinations of several enzymes with differ- Molecules marked with ubiquitin (“ubiquiti-
ent specificities are required for complete nated”) are recognized by the 19S particle,
degradation of proteins into free amino unfolded usingATP,and then shiftedinto
acids. Proteinases and peptidases are found the interior of the nucleus, where degradation
not only in the gastrointestinal tract (see takes place. Ubiquitin is not degraded, but is
p. 268), but also inside the cell (see below). reused after renewed activation.
The proteolytic enzymes are classified into
endopeptidases and exopeptidases,according
C. Serine proteases
to their site of attack in the substrate mole-
cule. The endopeptidases or proteinases cleave A large group of proteinases contain serine in
peptide bonds inside peptide chains. They their active center. The serine proteases in-
“recognize” and bind to short sections of the clude, for example, the digestive enzymes
substrate’s sequence, and then hydrolyze trypsin, chymotrypsin, and elastase (see
bonds between particular amino acid residues pp. 94 and 268), many coagulation factors
in a relatively specific way (see p. 94). The (see p. 290), and the fibrinolytic enzyme plas-
proteinases are classified according to their min and its activators (see p. 292).
reaction mechanism. In serine proteinases, As described on p. 270, pancreatic protein-
for example (see C), a serine residue in the ases are secreted as proenzymes (zymogens).
enzyme is important for catalysis, while in Activation of these is also based on proteolytic
cysteine proteinases, it is a cysteine residue, cleavages. This is illustrated here in detail us-
and so on. ing the example of trypsinogen,the precursor
The exopeptidases attack peptides from of trypsin (1). Activation of trypsinogen starts
their termini. Peptidases that act at the N with cleavage of an N-terminal hexapeptide
terminus are known as aminopeptidases, by enteropeptidase (enterokinase), a specific
while those that recognize the C terminus serine proteinase that is located in the mem-
are called carboxypeptidases.The dipepti- brane of the intestinal epithelium. The cleav-
dases only hydrolyze dipeptides. age product (β-trypsin) is already catalytically
active, and it cleaves additional trypsinogen
moleculesat the sitesmarkedin red in the
B. Proteasome
illustration (autocatalytic cleavage). The pre-
The functional proteins in the cell have to be cursors of chymotrypsin, elastase, and car-
protected in order to prevent premature deg- boxypeptidase A, among others, are also acti-
radation. Some of the intracellularly active vated by trypsin.
proteolytic enzymes are therefore enclosed The active center of trypsin is shown in
in lysosomes (see p. 234). The proteinases Fig. 2. A serine residue in the enzyme (Ser-
that act there are also known as cathepsins. 195), supported by a histidine residue and
Another carefully regulated system for pro- an aspartate residue (His-57, Asp-102), nucle-
tein degradation is located in the cytoplasm. ophilically attacks the bond that is to be
This consists of large protein complexes (mass cleaved(redarrow). Thecleavagesitein the
6
2 10 Da), the proteasomes.Proteasomes substrate peptide is located on the C-terminal
contain a barrel-shaped core consisting of 28 side of a lysine residue, the side chain of
subunits that has a sedimentation coef cient which is fixed in a special “binding pocket”
(see p. 200) of 20 S. Proteolytic activity of the enzyme (left) during catalysis (see
(shown here by the scissors) is localized in p. 94).
the interior of the 20-S core and is therefore
protected. The openings in the barrel are
sealed by 19-S particles with a complex struc-
ture that control access to the core.
Proteins destined for degradation in the
proteasome (e. g., incorrectly folded or old
Koolman, Color Atlas of Biochemistry, 2nd edition © 2005 Thieme
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