Dynamics and mechanistic interpretations of nonribosomal peptide synthetase cyclization domains

Andrew D. Gnann; Kenneth Marincin; Dominique P. Frueh; Daniel P. Dowling

doi:10.1016/j.cbpa.2022.102228

Dynamics and mechanistic interpretations of nonribosomal peptide synthetase cyclization domains

Andrew D. Gnann, Kenneth Marincin, Dominique P. Frueh, Daniel P. Dowling

School of Medicine

Research output: Contribution to journal › Review article › peer-review

Abstract

Ox-/thiazoline groups in nonribosomal peptides are formed by a variant of peptide-forming condensation domains called heterocyclization (Cy) domains and appear in a range of pharmaceutically important natural products and virulence factors. Recent cryo-EM, crystallographic, and NMR studies of Cy domains make it opportune to revisit outstanding questions regarding their molecular mechanisms. This review covers structural and dynamical findings about Cy domains that will inform future bioengineering efforts and our understanding of natural product synthesis.

Original language	English (US)
Article number	102228
Journal	Current Opinion in Chemical Biology
Volume	72
DOIs	https://doi.org/10.1016/j.cbpa.2022.102228
State	Published - Feb 2023

Keywords

Allostery
Bioengineering
Cyclodehydration
Heterocycle
Pantetheine
Protein–protein interactions

ASJC Scopus subject areas

Analytical Chemistry
Biochemistry

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10.1016/j.cbpa.2022.102228

Cite this

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title = "Dynamics and mechanistic interpretations of nonribosomal peptide synthetase cyclization domains",

abstract = "Ox-/thiazoline groups in nonribosomal peptides are formed by a variant of peptide-forming condensation domains called heterocyclization (Cy) domains and appear in a range of pharmaceutically important natural products and virulence factors. Recent cryo-EM, crystallographic, and NMR studies of Cy domains make it opportune to revisit outstanding questions regarding their molecular mechanisms. This review covers structural and dynamical findings about Cy domains that will inform future bioengineering efforts and our understanding of natural product synthesis.",

keywords = "Allostery, Bioengineering, Cyclodehydration, Heterocycle, Pantetheine, Protein–protein interactions",

author = "Gnann, {Andrew D.} and Kenneth Marincin and Frueh, {Dominique P.} and Dowling, {Daniel P.}",

note = "Funding Information: Support for this research was provided by the National Institute of General Medical Sciences ( NIGMS ) (1R15GM123425-01) to D.P.D., and A.D.G. was supported by a Sanofi Genzyme Doctoral Research Fellowship. D.P.F. acknowledges support from NIGMS R01 GM104257. Publisher Copyright: {\textcopyright} 2022 Elsevier Ltd",

year = "2023",

month = feb,

doi = "10.1016/j.cbpa.2022.102228",

language = "English (US)",

volume = "72",

journal = "Current Opinion in Chemical Biology",

issn = "1367-5931",

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AU - Gnann, Andrew D.

AU - Marincin, Kenneth

AU - Frueh, Dominique P.

AU - Dowling, Daniel P.

N1 - Funding Information: Support for this research was provided by the National Institute of General Medical Sciences ( NIGMS ) (1R15GM123425-01) to D.P.D., and A.D.G. was supported by a Sanofi Genzyme Doctoral Research Fellowship. D.P.F. acknowledges support from NIGMS R01 GM104257. Publisher Copyright: © 2022 Elsevier Ltd

PY - 2023/2

Y1 - 2023/2

N2 - Ox-/thiazoline groups in nonribosomal peptides are formed by a variant of peptide-forming condensation domains called heterocyclization (Cy) domains and appear in a range of pharmaceutically important natural products and virulence factors. Recent cryo-EM, crystallographic, and NMR studies of Cy domains make it opportune to revisit outstanding questions regarding their molecular mechanisms. This review covers structural and dynamical findings about Cy domains that will inform future bioengineering efforts and our understanding of natural product synthesis.

AB - Ox-/thiazoline groups in nonribosomal peptides are formed by a variant of peptide-forming condensation domains called heterocyclization (Cy) domains and appear in a range of pharmaceutically important natural products and virulence factors. Recent cryo-EM, crystallographic, and NMR studies of Cy domains make it opportune to revisit outstanding questions regarding their molecular mechanisms. This review covers structural and dynamical findings about Cy domains that will inform future bioengineering efforts and our understanding of natural product synthesis.

KW - Allostery

KW - Bioengineering

KW - Cyclodehydration

KW - Heterocycle

KW - Pantetheine

KW - Protein–protein interactions

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U2 - 10.1016/j.cbpa.2022.102228

DO - 10.1016/j.cbpa.2022.102228

M3 - Review article

C2 - 36402006

AN - SCOPUS:85141990149

SN - 1367-5931

VL - 72

JO - Current Opinion in Chemical Biology

JF - Current Opinion in Chemical Biology

M1 - 102228

ER -

Dynamics and mechanistic interpretations of nonribosomal peptide synthetase cyclization domains

Abstract

Keywords

ASJC Scopus subject areas

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