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PDBsum entry 2g0d
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Biosynthetic protein PDB id
2g0d

 

 

 

 

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Contents
Protein chain
404 a.a. *
Metals
_ZN
Waters ×262
* Residue conservation analysis
PDB id:
2g0d
Name: Biosynthetic protein
Title: Nisin cyclase
Structure: Nisin biosynthesis protein nisc. Chain: a. Engineered: yes
Source: Lactococcus lactis subsp. Lactis. Organism_taxid: 1360. Strain: subsp. Lactis. Gene: nisc. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Resolution:
2.21Å     R-factor:   0.190     R-free:   0.233
Authors: S.K.Nair
Key ref:
B.Li et al. (2006). Structure and mechanism of the lantibiotic cyclase involved in nisin biosynthesis. Science, 311, 1464-1467. PubMed id: 16527981 DOI: 10.1126/science.1121422
Date:
12-Feb-06     Release date:   23-May-06    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q03202  (NISC_LACLL) -  Nisin biosynthesis protein NisC from Lactococcus lactis subsp. lactis
Seq:
Struc: 		418 a.a.
404 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.?
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

 

 
DOI no: 10.1126/science.1121422 Science 311:1464-1467 (2006)
PubMed id: 16527981  
 
 
Structure and mechanism of the lantibiotic cyclase involved in nisin biosynthesis.
B.Li, J.P.Yu, J.S.Brunzelle, G.N.Moll, W.A.van der Donk, S.K.Nair.
 
  ABSTRACT  
 
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.
 
  Selected figure(s)  
 
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). 		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 figures are reprinted by permission from the AAAs: Science (2006, 311, 1464-1467) copyright 2006.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21182576 T.Kabuki, Y.Kawai, H.Uenishi, Y.Seto, J.Kok, H.Nakajima, and T.Saito (2011).
Gene cluster for biosynthesis of thermophilin 1277--a lantibiotic produced by Streptococcus thermophilus SBT1277, and heterologous expression of TepI, a novel immunity peptide.
  J Appl Microbiol, 110, 641-649.  
21114289 Y.Shi, X.Yang, N.Garg, and W.A.van der Donk (2011).
Production of Lantipeptides in Escherichia coli.
  J Am Chem Soc, 133, 2338-2341.  
21091497 D.Field, C.Hill, P.D.Cotter, and R.P.Ross (2010).
The dawning of a 'Golden era' in lantibiotic bioengineering.
  Mol Microbiol, 78, 1077-1087.  
20500830 D.H.Haft, M.K.Basu, and D.A.Mitchell (2010).
Expansion of ribosomally produced natural products: a nitrile hydratase- and Nif11-related precursor family.
  BMC Biol, 8, 70.  
20213184 G.Medaglia, and S.Panke (2010).
Development of a fermentation process based on a defined medium for the production of pregallidermin, a nontoxic precursor of the lantibiotic gallidermin.
  Appl Microbiol Biotechnol, 87, 145-157.  
20140513 G.N.Moll, A.Kuipers, and R.Rink (2010).
Microbial engineering of dehydro-amino acids and lanthionines in non-lantibiotic peptides.
  Antonie Van Leeuwenhoek, 97, 319-333.  
19915831 K.Shioya, Y.Harada, J.Nagao, J.Nakayama, and K.Sonomoto (2010).
Characterization of modification enzyme NukM and engineering of a novel thioether bridge in lantibiotic nukacin ISK-1.
  Appl Microbiol Biotechnol, 86, 891-899.  
20016494 T.J.Oman, and W.A.van der Donk (2010).
Follow the leader: the use of leader peptides to guide natural product biosynthesis.
  Nat Chem Biol, 6, 9.  
20351769 Y.Goto, B.Li, J.Claesen, Y.Shi, M.J.Bibb, and W.A.van der Donk (2010).
Discovery of unique lanthionine synthetases reveals new mechanistic and evolutionary insights.
  PLoS Biol, 8, e1000339.  
19286651 D.A.Mitchell, S.W.Lee, M.A.Pence, A.L.Markley, J.D.Limm, V.Nizet, and J.E.Dixon (2009).
Structural and functional dissection of the heterocyclic Peptide cytotoxin streptolysin s.
  J Biol Chem, 284, 13004-13012.  
19233656 D.F.Brennan, and D.Barford (2009).
Eliminylation: a post-translational modification catalyzed by phosphothreonine lyases.
  Trends Biochem Sci, 34, 108-114.  
19058272 E.M.Nolan, and C.T.Walsh (2009).
How nature morphs peptide scaffolds into antibiotics.
  Chembiochem, 10, 34-53.  
19202107 G.Liu, J.Zhong, J.Ni, M.Chen, H.Xiao, and L.Huan (2009).
Characteristics of the bovicin HJ50 gene cluster in Streptococcus bovis HJ50.
  Microbiology, 155, 584-593.  
19642421 J.A.McIntosh, M.S.Donia, and E.W.Schmidt (2009).
Ribosomal peptide natural products: bridging the ribosomal and nonribosomal worlds.
  Nat Prod Rep, 26, 537-559.  
19620240 J.Lubelski, R.Khusainov, and O.P.Kuipers (2009).
Directionality and coordination of dehydration and ring formation during biosynthesis of the lantibiotic nisin.
  J Biol Chem, 284, 25962-25972.  
19222036 M.R.Levengood, C.C.Kerwood, C.Chatterjee, and W.A.van der Donk (2009).
Investigation of the substrate specificity of lacticin 481 synthetase by using nonproteinogenic amino acids.
  Chembiochem, 10, 911-919.  
19663480 M.V.Lee, L.A.Ihnken, Y.O.You, A.L.McClerren, W.A.van der Donk, and N.L.Kelleher (2009).
Distributive and directional behavior of lantibiotic synthetases revealed by high-resolution tandem mass spectrometry.
  J Am Chem Soc, 131, 12258-12264.  
19929850 T.K.Attwood, D.B.Kell, P.McDermott, J.Marsh, S.R.Pettifer, and D.Thorne (2009).
Calling International Rescue: knowledge lost in literature and data landslide!
  Biochem J, 424, 317-333.  
19528316 W.Zhang, L.Wang, Y.Liu, J.Xu, G.Zhu, H.Cang, X.Li, M.Bartlam, K.Hensley, G.Li, Z.Rao, and X.C.Zhang (2009).
Structure of human lanthionine synthetase C-like protein 1 and its interaction with Eps8 and glutathione.
  Genes Dev, 23, 1387-1392.
PDB codes: 3e6u 3e73
18791001 A.Kuipers, J.Meijer-Wierenga, R.Rink, L.D.Kluskens, and G.N.Moll (2008).
Mechanistic dissection of the enzyme complexes involved in biosynthesis of lacticin 3147 and nisin.
  Appl Environ Microbiol, 74, 6591-6597.  
18827932 D.S.Glueck (2008).
Metal-catalyzed nucleophilic carbon-heteroatom (C-X) bond formation: the role of M-X intermediates.
  Dalton Trans, (), 5276-5286.  
18249199 D.W.Christianson (2008).
Unearthing the roots of the terpenome.
  Curr Opin Chem Biol, 12, 141-150.  
18570437 G.C.Patton, M.Paul, L.E.Cooper, C.Chatterjee, and W.A.van der Donk (2008).
The importance of the leader sequence for directing lanthionine formation in lacticin 481.
  Biochemistry, 47, 7342-7351.  
  19513236 J.G.Chen (2008).
Heterotrimeric G-protein signaling in Arabidopsis: Puzzling G-protein-coupled receptor.
  Plant Signal Behav, 3, 1042-1045.  
  19841654 J.G.Chen, and B.E.Ellis (2008).
GCR2 is a new member of the eukaryotic lanthionine synthetase component C-like protein family.
  Plant Signal Behav, 3, 307-310.  
18539792 J.Lubelski, W.Overkamp, L.D.Kluskens, G.N.Moll, and O.P.Kuipers (2008).
Influence of shifting positions of Ser, Thr, and Cys residues in prenisin on the efficiency of modification reactions and on the antimicrobial activities of the modified prepeptides.
  Appl Environ Microbiol, 74, 4680-4685.  
18570436 L.A.Furgerson Ihnken, C.Chatterjee, and W.A.van der Donk (2008).
In vitro reconstitution and substrate specificity of a lantibiotic protease.
  Biochemistry, 47, 7352-7363.  
18940665 L.E.Cooper, A.L.McClerren, A.Chary, and W.A.van der Donk (2008).
Structure-activity relationship studies of the two-component lantibiotic haloduracin.
  Chem Biol, 15, 1035-1045.  
18296644 M.Koutmos, R.Pejchal, T.M.Bomer, R.G.Matthews, J.L.Smith, and M.L.Ludwig (2008).
Metal active site elasticity linked to activation of homocysteine in methionine synthases.
  Proc Natl Acad Sci U S A, 105, 3286-3291.
PDB codes: 3bof 3bol 3bq5 3bq6
18294843 M.R.Levengood, and W.A.van der Donk (2008).
Use of lantibiotic synthetases for the preparation of bioactive constrained peptides.
  Bioorg Med Chem Lett, 18, 3025-3028.  
17096664 A.Dufour, T.Hindré, D.Haras, and J.P.Le Pennec (2007).
The biology of lantibiotics from the lacticin 481 group is coming of age.
  FEMS Microbiol Rev, 31, 134-167.  
17991845 C.A.Johnston, B.R.Temple, J.G.Chen, Y.Gao, E.N.Moriyama, A.M.Jones, D.P.Siderovski, and F.S.Willard (2007).
Comment on "A G protein coupled receptor is a plasma membrane receptor for the plant hormone abscisic acid".
  Science, 318, 914; author reply 914.  
17192080 G.Li, and W.A.van der Donk (2007).
Efficient synthesis of suitably protected beta-difluoroalanine and gamma-difluorothreonine from L-ascorbic acid.
  Org Lett, 9, 41-44.  
17506681 J.M.Willey, and W.A.van der Donk (2007).
Lantibiotics: peptides of diverse structure and function.
  Annu Rev Microbiol, 61, 477-501.  
17376731 J.Penner-Hahn (2007).
Zinc-promoted alkyl transfer: a new role for zinc.
  Curr Opin Chem Biol, 11, 166-171.  
17480057 M.Paul, G.C.Patton, and W.A.van der Donk (2007).
Mutants of the zinc ligands of lacticin 481 synthetase retain dehydration activity but have impaired cyclization activity.
  Biochemistry, 46, 6268-6276.  
17927474 N.I.Martin, and E.Breukink (2007).
Expanding role of lipid II as a target for lantibiotics.
  Future Microbiol, 2, 513-525.  
17377656 S.L.Cobb, and J.C.Vederas (2007).
A concise stereoselective synthesis of orthogonally protected lanthionine and beta-methyllanthionine.
  Org Biomol Chem, 5, 1031-1038.  
17650008 X.Zhang, W.Ni, and W.A.van der Donk (2007).
On the regioselectivity of thioether formation by lacticin 481 synthetase.
  Org Lett, 9, 3343-3346.  
17894782 Y.Gao, Q.Zeng, J.Guo, J.Cheng, B.E.Ellis, and J.G.Chen (2007).
Genetic characterization reveals no role for the reported ABA receptor, GCR2, in ABA control of seed germination and early seedling development in Arabidopsis.
  Plant J, 52, 1001-1013.  
17455908 Y.O.You, and W.A.van der Donk (2007).
Mechanistic investigations of the dehydration reaction of lacticin 481 synthetase using site-directed mutagenesis.
  Biochemistry, 46, 5991-6000.  
17041158 A.Kuipers, J.Wierenga, R.Rink, L.D.Kluskens, A.J.Driessen, O.P.Kuipers, and G.N.Moll (2006).
Sec-mediated transport of posttranslationally dehydrated peptides in Lactococcus lactis.
  Appl Environ Microbiol, 72, 7626-7633.  
17085596 A.L.McClerren, L.E.Cooper, C.Quan, P.M.Thomas, N.L.Kelleher, and W.A.van der Donk (2006).
Discovery and in vitro biosynthesis of haloduracin, a two-component lantibiotic.
  Proc Natl Acad Sci U S A, 103, 17243-17248.  
16771845 E.Breukink (2006).
A lesson in efficient killing from two-component lantibiotics.
  Mol Microbiol, 61, 271-273.  
16917798 G.Jung (2006).
Enzyme-catalyzed sulfide ring formation in lantibiotics.
  Angew Chem Int Ed Engl, 45, 5919-5921.  
17160060 J.Clardy, M.A.Fischbach, and C.T.Walsh (2006).
New antibiotics from bacterial natural products.
  Nat Biotechnol, 24, 1541-1550.  
17046525 J.Nagao, S.M.Asaduzzaman, Y.Aso, K.Okuda, J.Nakayama, and K.Sonomoto (2006).
Lantibiotics: insight and foresight for new paradigm.
  J Biosci Bioeng, 102, 139-149.  
16981206 L.Di Costanzo, L.V.Flores, and D.W.Christianson (2006).
Stereochemistry of guanidine-metal interactions: implications for L-arginine-metal interactions in protein structure and function.
  Proteins, 65, 637-642.  
17168571 W.A.van der Donk (2006).
Rings, radicals, and regeneration: the early years of a bioorganic laboratory.
  J Org Chem, 71, 9561-9571.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.

 

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