Structure and Mechanism of the Lantibiotic Cyclase Involved in Nisin Biosynthesis

American Association for the Advancement of Science (AAAS) - Tập 311 Số 5766 - Trang 1464-1467 - 2006
Бо Ли1,2,3,4,5, John‐Paul J. Yu1,2,4,5, J.S. Brunzelle1,2,3,4,5, Gert N. Moll1,2,3,4,5, Wilfred A. van der Donk1,2,3,4,5, Satish K. Nair1,2,3,5
1BiOMaDe Technology Foundation, Groningen, Netherlands.
2Center for Biophysics and Computational Biology, University of Illinois at Urbana-Champaign, 600 South Mathews Avenue, Urbana, IL 61801, USA
3Department of Biochemistry, University of Illinois at Urbana-Champaign, 600 South Mathews Avenue, Urbana, IL 61801, USA
4Department of Chemistry, University of Illinois at Urbana-Champaign, 600 South Mathews Avenue, Urbana, IL, 61801, USA
5Life Sciences Collaborative Access Team, Argonne National Labs, Argonne, IL, 60439, USA.

Tóm tắt

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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Single-letter abbreviations for the amino acid residues are as follows: A Ala; C Cys; D Asp; E Glu; F Phe; G Gly; H His; I Ile; K Lys; L Leu; M Met; N Asn; P Pro; Q Gln; R Arg; S Ser; T Thr; V Val; W Trp; and Y Tyr.

The structures have been deposited in the Protein Data Bank with the following accession codes: 2G02 (native NisC) and 2G0D (NisC with lead). This work was supported by the NIH (grant GM58822 to W.A.V.) and by the University of Illinois. J.J.Y. was supported by the Molecular Biophysics Training Grant (NIH) and by a National Research Service Award from the National Institute on Drug Abuse. We thank E. de Boef (BiOMaDe) for technical assistance and R. Matthews for helpful discussions.

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American Association for the Advancement of Science (AAAS)

Tập 311 Số 5766

1464-1467

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