St Andrews Research Repository

St Andrews University Home
View Item 
  •   St Andrews Research Repository
  • University of St Andrews Research
  • University of St Andrews Research
  • University of St Andrews Research
  • View Item
  •   St Andrews Research Repository
  • University of St Andrews Research
  • University of St Andrews Research
  • University of St Andrews Research
  • View Item
  •   St Andrews Research Repository
  • University of St Andrews Research
  • University of St Andrews Research
  • University of St Andrews Research
  • View Item
  • Login
JavaScript is disabled for your browser. Some features of this site may not work without it.

Bypassing the requirement for aminoacyl-tRNA by a cyclodipeptide synthase enzyme

Thumbnail
View/Open
Harding_2021_RSCCB_Bypassing_CC.pdf (4.364Mb)
Date
15/01/2021
Author
Harding, Christopher John
Sutherland, Emmajay
Hanna, Jane
Houston, Douglas
Melo Czekster, Clarissa
Keywords
QH301 Biology
DAS
Metadata
Show full item record
Abstract
Cyclodipeptide synthases (CDPSs) produce a variety of cyclic dipeptide products by utilising two aminoacylated tRNA substrates. We sought to investigate the minimal requirements for substrate usage in this class of enzymes as the relationship between CDPSs and their substrates remains elusive. Here, we investigated the Bacillus thermoamylovorans enzyme, BtCDPS, which synthesises cyclo(L-Leu–L-Leu). We systematically tested where specificity arises and, in the process, uncovered small molecules (activated amino esters) that will suffice as substrates, although catalytically poor. We solved the structure of BtCDPS to 1.7 Å and combining crystallography, enzymatic assays and substrate docking experiments propose a model for how the minimal substrates interact with the enzyme. This work is the first report of a CDPS enzyme utilizing a molecule other than aa-tRNA as a substrate; providing insights into substrate requirements and setting the stage for the design of improved simpler substrates.
Citation
Harding , C J , Sutherland , E , Hanna , J , Houston , D & Melo Czekster , C 2021 , ' Bypassing the requirement for aminoacyl-tRNA by a cyclodipeptide synthase enzyme ' , RSC Chemical Biology , vol. Advance article . https://doi.org/10.1039/D0CB00142B
Publication
RSC Chemical Biology
Status
Peer reviewed
DOI
https://doi.org/10.1039/D0CB00142B
ISSN
2633-0679
Type
Journal article
Rights
Copyright © 2021 The Author(s). Open Access. This article is licensed under a Creative Commons Attribution 3.0 Unported Licence.
Description
C. J. H. and C. M. C. are funded by the Wellcome trust (210486/Z/18/Z), ES is funded by the Cunningham trust (PhD-CT-18-41).
Collections
  • University of St Andrews Research
URI
http://hdl.handle.net/10023/21283

Items in the St Andrews Research Repository are protected by copyright, with all rights reserved, unless otherwise indicated.

Advanced Search

Browse

All of RepositoryCommunities & CollectionsBy Issue DateNamesTitlesSubjectsClassificationTypeFunderThis CollectionBy Issue DateNamesTitlesSubjectsClassificationTypeFunder

My Account

Login

Open Access

To find out how you can benefit from open access to research, see our library web pages and Open Access blog. For open access help contact: openaccess@st-andrews.ac.uk.

Accessibility

Read our Accessibility statement.

How to submit research papers

The full text of research papers can be submitted to the repository via Pure, the University's research information system. For help see our guide: How to deposit in Pure.

Electronic thesis deposit

Help with deposit.

Repository help

For repository help contact: Digital-Repository@st-andrews.ac.uk.

Give Feedback

Cookie policy

This site may use cookies. Please see Terms and Conditions.

Usage statistics

COUNTER-compliant statistics on downloads from the repository are available from the IRUS-UK Service. Contact us for information.

© University of St Andrews Library

University of St Andrews is a charity registered in Scotland, No SC013532.

  • Facebook
  • Twitter