Figure 4.
Fig. 4. Proposed mechanism for the cyclization reaction
catalyzed by NisC illustrated for the formation of the B ring of
nisin. Upon binding of the dehydrated peptide, the sulfur of a
Cys residue targeted for cyclization displaces the water from
the Zn2+ ion and is deprotonated by an active site base or
water. Coordination of cysteine to Zn in farnesyl transferase
lowers its pK[a] to 6.4 (25); hence, a protein-derived base is
not absolutely required. Attack of the thiolate onto the ß
carbon of Dhb generates an enolate intermediate that is
protonated to provide the D-configuration at the carbon. Because
the stereochemistry of the addition is anti, the active site
base that deprotonates Cys must be different from the acid that
protonates the enolate. Arg280 might activate a water molecule
or could fulfill a different role such as activation of the
carbonyl of Dha/Dhb.
The above figure is reprinted
by permission from the AAAs:
Science
(2006,
311,
1464-1467)
copyright 2006.
carbon. Because
the stereochemistry of the addition is anti, the active site
base that deprotonates Cys must be different from the acid that
protonates the enolate. Arg280 might activate a water molecule
or could fulfill a different role such as activation of the
carbonyl of Dha/Dhb.