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PDBsum entry 2g0d
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Biosynthetic protein
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PDB id
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2g0d
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References listed in PDB file
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Key reference
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Title
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Structure and mechanism of the lantibiotic cyclase involved in nisin biosynthesis.
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Authors
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B.Li,
J.P.Yu,
J.S.Brunzelle,
G.N.Moll,
W.A.Van der donk,
S.K.Nair.
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Ref.
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Science, 2006,
311,
1464-1467.
[DOI no: ]
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PubMed id
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Abstract
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Nisin is a posttranslationally modified antimicrobial peptide that is widely
used as a food preservative. It contains five cyclic thioethers of varying sizes
that are installed by a single enzyme, NisC. Reported here are the in vitro
reconstitution of the cyclization process and the x-ray crystal structure of the
NisC enzyme. The structure reveals similarities in fold and substrate activation
with mammalian farnesyl transferases, suggesting that human homologs of NisC
posttranslationally modify a cysteine of a protein substrate.
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Figure 2.
Fig. 2. (A) A view perpendicular to the  , barrel, showing
the disposition of the zinc ion and the extended domain. (B)
View down the spindle axis of the toroid showing the relative
positions of seven sets of helices. The
catalytic zinc ion is located near the center of the toroid
adjacent to the extended domain. The figures were created with
Ribbons software (33).
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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.
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The above figures are
reprinted
by permission from the AAAs:
Science
(2006,
311,
1464-1467)
copyright 2006.
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