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.

Structural analysis of leader peptide binding enables leader-free cyanobactin processing

Thumbnail
View/Open
Naismith_2015_NCb_Structural_AM.pdf (2.973Mb)
Date
08/2015
Author
Koehnke, Jesko Alexander Johannes Gunter
Mann, Greg
Bent, Andrew Frank
Ludewig, Hannes
Shirran, Sally Lorna
Botting, Catherine Helen
Lebl, Tomas
Houssen, Wael
Jaspers, Marcel
Naismith, Jim
Funder
BBSRC
Grant ID
BB/K015508/1
Keywords
QD Chemistry
NDAS
BDC
R2C
Metadata
Show full item record
Altmetrics Handle Statistics
Altmetrics DOI Statistics
Abstract
Regioselective modification of amino acids within the context of a peptide is common to a number of biosynthetic pathways, and many of the resulting products have potential as therapeutics. The ATP-dependent enzyme LynD heterocyclizes multiple cysteine residues to thiazolines within a peptide substrate. The enzyme requires the substrate to have a conserved N-terminal leader for full activity. Catalysis is almost insensitive to immediately flanking residues in the substrate, suggesting that recognition occurs distant from the active site. Nucleotide and peptide substrate co-complex structures of LynD reveal that the substrate leader peptide binds to and extends the β-sheet of a conserved domain of LynD, whereas catalysis is accomplished in another conserved domain. The spatial segregation of catalysis from recognition combines seemingly contradictory properties of regioselectivity and promiscuity, and it appears to be a conserved strategy in other peptide-modifying enzymes. A variant of LynD that efficiently processes substrates without a leader peptide has been engineered.
Citation
Koehnke , J A J G , Mann , G , Bent , A F , Ludewig , H , Shirran , S L , Botting , C H , Lebl , T , Houssen , W , Jaspers , M & Naismith , J 2015 , ' Structural analysis of leader peptide binding enables leader-free cyanobactin processing ' , Nature Chemical Biology , vol. 11 , no. 8 , pp. 558-563 . https://doi.org/10.1038/nchembio.1841
Publication
Nature Chemical Biology
Status
Peer reviewed
DOI
https://doi.org/10.1038/nchembio.1841
ISSN
1552-4450
Type
Journal article
Rights
© 2014. Macmillan Publishers Limited. All rights reserved. NPG Terms of reuse of archived manuscipts applies http://www.nature.com/authors/policies/license.html
Description
This work was supported by grants from the ERC 339367 (J.H.N. and M.J.) and BBSRC BB/K015508/1 (J.H.N and M.J.). We acknowledge use of the Diamond (beamlines I02 and I24) and ESRF (beamline ID29) synchrotrons. JHN is Royal Society Wolfson Merit Award Holder and a 1000 talent scholar of the Chinese Government at Sichuan University.
Collections
  • University of St Andrews Research
URI
http://hdl.handle.net/10023/10008

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