3-phosphoglycerate
family: Cysteine (C)
General
features
R group:
-(CH2)-SH
Molecular
mass: 121.16 g/mol
R-group
pKa: 8.5
Physiological
roles
Cysteine
has several structural and catalytic roles: protein structure (disulfide bond
formation for stability when secreted), cysteine proteases (big contributor to
virulence), antioxidant properties (glutathione), iron-sulfur complexes, PPP
reactions (transketolase contains coenzyme B1/thiamine. The sulfur in the thiazole
ring functional group, which is crucial for catalytic function, is derived from
cysteine.)
Thiazole
synthesis:
A good
diagram may be found here:
Disulfide bond formation:
Disulfide bonds are highly useful
for protein structure, particularly because unlike all the other sidechain
interactions that contribute to secondary and tertiary structure, disulfide
bridges are covalent linkages, not distance dependent electrostatic and van der
Waal forces. Disulfide bonds are ideal for secreted proteins because the
physically hold protein folds in position (obvious) but the bridge stability is
pH dependent like the other noncovalent interactions. Reducing environments can
begin to reduce (and break) disulfide bonds at pH 7, but relative rates vary for
given solutions and microenvironments. For a ‘test-tube’ demonstration, look at
the kinetic analysis of reductive potential of isolated proteins in solutions
with various dithiols, DMH, BMS, DTT:
Cysteine protease activity: One
mode of peptide bond cleavage.
The
mechanism of a cysteine protease:
These
proteases use a conserved histidine residue to aid in their peptide bond
attack. Once the acyl-enzyme intermediate is formed (with one portion of the
previously intact protein released with a new free amino group) the Histidine
aids in the release of the second portion of the cleaved protein. The histidine
will pull a proton from a ambient water to generate a reactive –OH, this will
attack the ‘vulnerable’ carbonyl carbon of the thioacyl intermediate (pictured
on the far right).
Cysteine
proteases specific for host cell zymogens are particularly important virulence
factors for many bacteria, including those of Staphylococcus aureus and Streptococcus pyogenes. For example, details
on S. pyogenes’ SpeB protein can be
found here: http://mic.sgmjournals.org/content/150/5/1559.full
Glutathione
synthesis:
After cysteine and glutamine have been linked via the
gamma (amide-containing carbon of glutamine) an ATP is used to activate a
glycine that forms a peptide linkage to with carboxyl group of cysteine.
Proposed
antioxidant roles of glutathione (Pittman, Robinson, Poole, 2004) :
Generally
speaking, glutathione is used in the cell as protection from free radical
damage, using the sulfhydryl groups of adjacent cysteine residues of adjacent
glutathione molecules. A disulfide
bridge can be formed from two previously reduced cysteine residues contributing
two electrons to two free radicals.
In
the figure above, the oxidized glutathione is generated a couple ways, by DsbC
(a disulfide bond forming enzyme) and by other proteins that may or may not
have radicals but use the reducing power of glutathione. The regeneration of
reduced glutathione is not well-understood in bacteria.
Synthesis
Figure
3 from Lithgow, et al. (2004) helps define cyteine’s role in sulfur acquisition
in Escherichia coli and Bacillus subtilis. Sulfur can be
translocated into the cell in various forms by various transporters, but
ultimately, when inorganic sulfur is incorporated into cysteine (left side of
the figure), some intermediate, sulfur is added either in S2O3- form or S2-
form to O-acetylserine (OAS) which is generated by adding an acetyl group (COCH3) to the hydroxyl group of serine’s
sidechain.
O-acetylserine
shown here at chemspider http://www.chemspider.com/ImageView.aspx?id=184
The
general reaction may be found here in scheme 1 http://www.sciencedirect.com/science/article/pii/S0003986104004552
No comments:
Post a Comment