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Insights into the mechanism of the cyanobactin heterocyclase enzyme

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Insights into the mechanism of the cyanobactin heterocyclase enzyme. / Ge, Ying; Czekster, Clarissa Melo; Miller, Ona K.; Botting, Catherine H.; Schwarz-Linek, Ulrich; Naismith, James H.

In: Biochemistry, Vol. 58, No. 16, 23.04.2019, p. 2125-2132.

Research output: Contribution to journalArticle

Harvard

Ge, Y, Czekster, CM, Miller, OK, Botting, CH, Schwarz-Linek, U & Naismith, JH 2019, 'Insights into the mechanism of the cyanobactin heterocyclase enzyme' Biochemistry, vol. 58, no. 16, pp. 2125-2132. https://doi.org/10.1021/acs.biochem.9b00084

APA

Ge, Y., Czekster, C. M., Miller, O. K., Botting, C. H., Schwarz-Linek, U., & Naismith, J. H. (2019). Insights into the mechanism of the cyanobactin heterocyclase enzyme. Biochemistry, 58(16), 2125-2132. https://doi.org/10.1021/acs.biochem.9b00084

Vancouver

Ge Y, Czekster CM, Miller OK, Botting CH, Schwarz-Linek U, Naismith JH. Insights into the mechanism of the cyanobactin heterocyclase enzyme. Biochemistry. 2019 Apr 23;58(16):2125-2132. https://doi.org/10.1021/acs.biochem.9b00084

Author

Ge, Ying ; Czekster, Clarissa Melo ; Miller, Ona K. ; Botting, Catherine H. ; Schwarz-Linek, Ulrich ; Naismith, James H. / Insights into the mechanism of the cyanobactin heterocyclase enzyme. In: Biochemistry. 2019 ; Vol. 58, No. 16. pp. 2125-2132.

Bibtex - Download

@article{e9ece5d48cf44c77ae75208d653d6abb,
title = "Insights into the mechanism of the cyanobactin heterocyclase enzyme",
abstract = "Cyanobactin heterocyclases share the same catalytic domain (YcaO) as heterocyclases/cyclodehydratases from other ribosomal peptide (RiPPs) biosynthetic pathways. These enzymes process multiple residues (Cys/Thr/Ser) within the same substrate. The processing of cysteine residues proceeds with a known order. We show the order of reaction for threonines is different and depends in part on a leader peptide within the substrate. In contrast to other YcaO domains, which have been reported to exclusively break down ATP into ADP and inorganic phosphate, cyanobactin heterocyclases have been observed to produce AMP and inorganic pyrophosphate during catalysis. We dissect the nucleotide profiles associated with heterocyclization and propose a unifying mechanism, where the γ-phosphate of ATP is transferred in a kinase mechanism to the substrate to yield a phosphorylated intermediate common to all YcaO domains. In cyanobactin heterocyclases, this phosphorylated intermediate, in a proportion of turnovers, reacts with ADP to yield AMP and pyrophosphate.",
author = "Ying Ge and Czekster, {Clarissa Melo} and Miller, {Ona K.} and Botting, {Catherine H.} and Ulrich Schwarz-Linek and Naismith, {James H.}",
note = "The work is supported by the European Research Council NCB-TNT (339367), Biotechnology and Biological Sciences Research Council (BB/K015508/1 and BB/M001679/1).",
year = "2019",
month = "4",
day = "23",
doi = "10.1021/acs.biochem.9b00084",
language = "English",
volume = "58",
pages = "2125--2132",
journal = "Biochemistry",
issn = "0006-2960",
publisher = "American Chemical Society (ACS)",
number = "16",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - Insights into the mechanism of the cyanobactin heterocyclase enzyme

AU - Ge, Ying

AU - Czekster, Clarissa Melo

AU - Miller, Ona K.

AU - Botting, Catherine H.

AU - Schwarz-Linek, Ulrich

AU - Naismith, James H.

N1 - The work is supported by the European Research Council NCB-TNT (339367), Biotechnology and Biological Sciences Research Council (BB/K015508/1 and BB/M001679/1).

PY - 2019/4/23

Y1 - 2019/4/23

N2 - Cyanobactin heterocyclases share the same catalytic domain (YcaO) as heterocyclases/cyclodehydratases from other ribosomal peptide (RiPPs) biosynthetic pathways. These enzymes process multiple residues (Cys/Thr/Ser) within the same substrate. The processing of cysteine residues proceeds with a known order. We show the order of reaction for threonines is different and depends in part on a leader peptide within the substrate. In contrast to other YcaO domains, which have been reported to exclusively break down ATP into ADP and inorganic phosphate, cyanobactin heterocyclases have been observed to produce AMP and inorganic pyrophosphate during catalysis. We dissect the nucleotide profiles associated with heterocyclization and propose a unifying mechanism, where the γ-phosphate of ATP is transferred in a kinase mechanism to the substrate to yield a phosphorylated intermediate common to all YcaO domains. In cyanobactin heterocyclases, this phosphorylated intermediate, in a proportion of turnovers, reacts with ADP to yield AMP and pyrophosphate.

AB - Cyanobactin heterocyclases share the same catalytic domain (YcaO) as heterocyclases/cyclodehydratases from other ribosomal peptide (RiPPs) biosynthetic pathways. These enzymes process multiple residues (Cys/Thr/Ser) within the same substrate. The processing of cysteine residues proceeds with a known order. We show the order of reaction for threonines is different and depends in part on a leader peptide within the substrate. In contrast to other YcaO domains, which have been reported to exclusively break down ATP into ADP and inorganic phosphate, cyanobactin heterocyclases have been observed to produce AMP and inorganic pyrophosphate during catalysis. We dissect the nucleotide profiles associated with heterocyclization and propose a unifying mechanism, where the γ-phosphate of ATP is transferred in a kinase mechanism to the substrate to yield a phosphorylated intermediate common to all YcaO domains. In cyanobactin heterocyclases, this phosphorylated intermediate, in a proportion of turnovers, reacts with ADP to yield AMP and pyrophosphate.

U2 - 10.1021/acs.biochem.9b00084

DO - 10.1021/acs.biochem.9b00084

M3 - Article

VL - 58

SP - 2125

EP - 2132

JO - Biochemistry

T2 - Biochemistry

JF - Biochemistry

SN - 0006-2960

IS - 16

ER -

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ID: 258964229