schliessen

Filtern

 

Bibliotheken

Structure of a modular polyketide synthase

Polyketide natural products constitute a broad class of compounds with diverse structural features and biological activities. Their biosynthetic machinery, represented by type I polyketide synthases (PKSs), has an architecture in which successive modules catalyse two-carbon linear extensions and ket... Full description

Journal Title: Nature 2014, Vol.510(7506), p.512
Main Author: Somnath Dutta
Other Authors: Jonathan R. Whicher , Douglas A. Hansen , Wendi A. Hale , Joseph A. Chemler , Grady R. Congdon , Alison R. H. Narayan , Kristina Håkansson , David H. Sherman , Janet L. Smith , Georgios Skiniotis
Format: Electronic Article Electronic Article
Language:
Subjects:
ID: ISSN: 0028-0836 ; E-ISSN: 1476-4687 ; DOI: 10.1038/nature13423
Link: http://dx.doi.org/10.1038/nature13423
Zum Text:
SendSend as email Add to Book BagAdd to Book Bag
Staff View
recordid: nature_a10.1038/nature13423
title: Structure of a modular polyketide synthase
format: Article
creator:
  • Somnath Dutta
  • Jonathan R. Whicher
  • Douglas A. Hansen
  • Wendi A. Hale
  • Joseph A. Chemler
  • Grady R. Congdon
  • Alison R. H. Narayan
  • Kristina Håkansson
  • David H. Sherman
  • Janet L. Smith
  • Georgios Skiniotis
subjects:
  • Polyketides – Physiological Aspects
  • Polyketides – Structure
  • Protein Structure – Observations
ispartof: Nature, 2014, Vol.510(7506), p.512
description: Polyketide natural products constitute a broad class of compounds with diverse structural features and biological activities. Their biosynthetic machinery, represented by type I polyketide synthases (PKSs), has an architecture in which successive modules catalyse two-carbon linear extensions and keto-group processing reactions on intermediates covalently tethered to carrier domains. Here we used electron cryo-microscopy to determine sub-nanometre-resolution three-dimensional reconstructions of a full-length PKS module from the bacterium Streptomyces venezuelae that revealed an unexpectedly different architecture compared to the homologous dimeric mammalian fatty acid synthase. A single reaction chamber provides access to all catalytic sites for the intramodule carrier domain. In contrast, the carrier from the preceding module uses a separate entrance outside the reaction chamber to deliver the upstream polyketide intermediate for subsequent extension and modification. This study reveals for the first time, to our knowledge, the structural basis for both intramodule and intermodule substrate transfer in polyketide synthases, and establishes a new model for molecular dissection of these multifunctional enzyme systems.
language:
source:
identifier: ISSN: 0028-0836 ; E-ISSN: 1476-4687 ; DOI: 10.1038/nature13423
fulltext: fulltext
issn:
  • 0028-0836
  • 00280836
  • 1476-4687
  • 14764687
url: Link


@attributes
ID337692764
RANK0.07
NO1
SEARCH_ENGINEprimo_central_multiple_fe
SEARCH_ENGINE_TYPEPrimo Central Search Engine
LOCALfalse
PrimoNMBib
record
control
sourcerecordid10.1038/nature13423
sourceidnature_a
recordidTN_nature_a10.1038/nature13423
sourcesystemPC
pqid1544417337
galeid463819837
display
typearticle
titleStructure of a modular polyketide synthase
creatorSomnath Dutta ; Jonathan R. Whicher ; Douglas A. Hansen ; Wendi A. Hale ; Joseph A. Chemler ; Grady R. Congdon ; Alison R. H. Narayan ; Kristina Håkansson ; David H. Sherman ; Janet L. Smith ; Georgios Skiniotis
ispartofNature, 2014, Vol.510(7506), p.512
identifier
source
subjectPolyketides – Physiological Aspects ; Polyketides – Structure ; Protein Structure – Observations;
descriptionPolyketide natural products constitute a broad class of compounds with diverse structural features and biological activities. Their biosynthetic machinery, represented by type I polyketide synthases (PKSs), has an architecture in which successive modules catalyse two-carbon linear extensions and keto-group processing reactions on intermediates covalently tethered to carrier domains. Here we used electron cryo-microscopy to determine sub-nanometre-resolution three-dimensional reconstructions of a full-length PKS module from the bacterium Streptomyces venezuelae that revealed an unexpectedly different architecture compared to the homologous dimeric mammalian fatty acid synthase. A single reaction chamber provides access to all catalytic sites for the intramodule carrier domain. In contrast, the carrier from the preceding module uses a separate entrance outside the reaction chamber to deliver the upstream polyketide intermediate for subsequent extension and modification. This study reveals for the first time, to our knowledge, the structural basis for both intramodule and intermodule substrate transfer in polyketide synthases, and establishes a new model for molecular dissection of these multifunctional enzyme systems.
version7
lds50peer_reviewed
links
openurl$$Topenurl_article
backlink$$Uhttp://dx.doi.org/10.1038/nature13423$$EView_this_record_in_Nature
openurlfulltext$$Topenurlfull_article
search
creatorcontrib
0Somnath Dutta
1Jonathan R. Whicher
2Douglas A. Hansen
3Wendi A. Hale
4Joseph A. Chemler
5Grady R. Congdon
6Alison R. H. Narayan
7Kristina Håkansson
8David H. Sherman
9Janet L. Smith
10Georgios Skiniotis
titleStructure of a modular polyketide synthase
general
0Nature Publishing Group
110.1038/nature13423
2nature.com (Nature Publishing Group)
sourceidnature_a
recordidnature_a10.1038/nature13423
issn
00028-0836
100280836
21476-4687
314764687
rsrctypearticle
creationdate2014
searchscopenature_a
scopenature_a
lsr30VSR-Enriched:[pqid, subject, description, eissn, galeid, pages]
sort
titleStructure of a modular polyketide synthase
authorSomnath Dutta ; Jonathan R. Whicher ; Douglas A. Hansen ; Wendi A. Hale ; Joseph A. Chemler ; Grady R. Congdon ; Alison R. H. Narayan ; Kristina Håkansson ; David H. Sherman ; Janet L. Smith ; Georgios Skiniotis
creationdate20140618
facets
frbrgroupid-1701255290984434156
frbrtype5
creationdate2014
collectionnature.com (Nature Publishing Group)
prefilterarticles
rsrctypearticles
creatorcontrib
0Somnath Dutta
1Jonathan R. Whicher
2Douglas A. Hansen
3Wendi A. Hale
4Joseph A. Chemler
5Grady R. Congdon
6Alison R. H. Narayan
7Kristina Håkansson
8David H. Sherman
9Janet L. Smith
10Georgios Skiniotis
jtitleNature
toplevelpeer_reviewed
delivery
delcategoryRemote Search Resource
fulltextfulltext
addata
au
0Somnath Dutta
1Jonathan R. Whicher
2Douglas A. Hansen
3Wendi A. Hale
4Joseph A. Chemler
5Grady R. Congdon
6Alison R. H. Narayan
7Kristina Håkansson
8David H. Sherman
9Janet L. Smith
10Georgios Skiniotis
atitleStructure of a modular polyketide synthase
jtitleNature
risdate20140618
volume510
issue7506
spage512
issn0028-0836
genrearticle
ristypeJOUR
pubNature Publishing Group
doi10.1038/nature13423
pages512-517
eissn14764687
date2014-06-18