Structure of the epimerization domain of tyrocidine synthetase A

Publication type:
Journal article
Metadata:
Autoren
  • Stefan A Samel
  • Paul Czodrowski
  • Lars-Oliver Essen
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000335952500025&DestLinkType=FullRecord&DestApp=WOS_CPL
DOI
10.1107/S1399004714004398
Externe Identifier
  • Clarivate Analytics Document Solution ID: AH2LI
  • PubMed Identifier: 24816112
ISSN
2059-7983
Zeitschrift
ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY
Paginierung
1442 - 1452
Datum der Veröffentlichung
2014
Status
Published
Titel
Structure of the epimerization domain of tyrocidine synthetase A
Sub types
  • Article
Ausgabe der Zeitschrift
70

Data source: Web of Science (Lite)

Other metadata sources:
Abstract
<jats:p>Tyrocidine, a macrocyclic decapeptide from<jats:italic>Bacillus brevis</jats:italic>, is nonribosomally assembled by a set of multimodular peptide synthetases, which condense two D-amino acids and eight L-amino acids to produce this membrane-disturbing antibiotic. D-Phenylalanine, the first amino acid incorporated into tyrocidine, is catalytically derived from enzyme-bound L-Phe by the C-terminal epimerization (E) domain of tyrocidine synthetase A (TycA). The 1.5 Å resolution structure of the cofactor-independent TycA E domain reveals an intimate relationship to the condensation (C) domains of peptide synthetases. In contrast to the latter, the TycA E domain uses an enlarged bridge region to plug the active-site canyon from the acceptor side, whereas at the donor side a latch-like floor loop is suitably extended to accommodate the αIII helix of the preceding peptide-carrier domain. Additionally, E domains exclusively harbour a conserved glutamate residue, Glu882, that is opposite the active-site residue His743. This active-site topology implies Glu882 as a candidate acid–base catalyst, whereas His743 stabilizes in the protonated state a transient enolate intermediate of the L↔D isomerization.</jats:p>
Autoren
  • Stefan A Samel
  • Paul Czodrowski
  • Lars-Oliver Essen
DOI
10.1107/s1399004714004398
eISSN
1399-0047
Ausgabe der Veröffentlichung
5
Zeitschrift
Acta Crystallographica Section D Biological Crystallography
Online publication date
2014
Paginierung
1442 - 1452
Datum der Veröffentlichung
2014
Status
Published
Herausgeber
International Union of Crystallography (IUCr)
Herausgeber URL
http://dx.doi.org/10.1107/s1399004714004398
Datum der Datenerfassung
2022
Titel
Structure of the epimerization domain of tyrocidine synthetase A
Ausgabe der Zeitschrift
70

Data source: Crossref

Abstract
Tyrocidine, a macrocyclic decapeptide from Bacillus brevis, is nonribosomally assembled by a set of multimodular peptide synthetases, which condense two D-amino acids and eight L-amino acids to produce this membrane-disturbing antibiotic. D-Phenylalanine, the first amino acid incorporated into tyrocidine, is catalytically derived from enzyme-bound L-Phe by the C-terminal epimerization (E) domain of tyrocidine synthetase A (TycA). The 1.5 Å resolution structure of the cofactor-independent TycA E domain reveals an intimate relationship to the condensation (C) domains of peptide synthetases. In contrast to the latter, the TycA E domain uses an enlarged bridge region to plug the active-site canyon from the acceptor side, whereas at the donor side a latch-like floor loop is suitably extended to accommodate the αIII helix of the preceding peptide-carrier domain. Additionally, E domains exclusively harbour a conserved glutamate residue, Glu882, that is opposite the active-site residue His743. This active-site topology implies Glu882 as a candidate acid-base catalyst, whereas His743 stabilizes in the protonated state a transient enolate intermediate of the L↔D isomerization.
Addresses
  • Biomedical Research Centre/FB15, Philipps Universität, Hans-Meerwein-Strasse 4, 35032 Marburg, Germany.
Autoren
  • Stefan A Samel
  • Paul Czodrowski
  • Lars-Oliver Essen
DOI
10.1107/s1399004714004398
eISSN
1399-0047
Externe Identifier
  • PubMed Identifier: 24816112
Open access
false
ISSN
0907-4449
Ausgabe der Veröffentlichung
Pt 5
Zeitschrift
Acta crystallographica. Section D, Biological crystallography
Schlüsselwörter
  • Bacillus
  • Peptide Synthases
  • Glutamic Acid
  • Crystallography, X-Ray
  • Catalytic Domain
  • Protein Structure, Tertiary
  • Models, Molecular
Sprache
eng
Medium
Print-Electronic
Online publication date
2014
Paginierung
1442 - 1452
Datum der Veröffentlichung
2014
Status
Published
Datum der Datenerfassung
2014
Titel
Structure of the epimerization domain of tyrocidine synthetase A.
Sub types
  • Research Support, Non-U.S. Gov't
  • Journal Article
Ausgabe der Zeitschrift
70

Data source: Europe PubMed Central

Abstract
Tyrocidine, a macrocyclic decapeptide from Bacillus brevis, is nonribosomally assembled by a set of multimodular peptide synthetases, which condense two D-amino acids and eight L-amino acids to produce this membrane-disturbing antibiotic. D-Phenylalanine, the first amino acid incorporated into tyrocidine, is catalytically derived from enzyme-bound L-Phe by the C-terminal epimerization (E) domain of tyrocidine synthetase A (TycA). The 1.5 Å resolution structure of the cofactor-independent TycA E domain reveals an intimate relationship to the condensation (C) domains of peptide synthetases. In contrast to the latter, the TycA E domain uses an enlarged bridge region to plug the active-site canyon from the acceptor side, whereas at the donor side a latch-like floor loop is suitably extended to accommodate the αIII helix of the preceding peptide-carrier domain. Additionally, E domains exclusively harbour a conserved glutamate residue, Glu882, that is opposite the active-site residue His743. This active-site topology implies Glu882 as a candidate acid-base catalyst, whereas His743 stabilizes in the protonated state a transient enolate intermediate of the L↔D isomerization.
Date of acceptance
2014
Autoren
  • Stefan A Samel
  • Paul Czodrowski
  • Lars-Oliver Essen
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/24816112
DOI
10.1107/S1399004714004398
eISSN
1399-0047
Ausgabe der Veröffentlichung
Pt 5
Zeitschrift
Acta Crystallogr D Biol Crystallogr
Schlüsselwörter
  • cofactor-independent epimerization
  • enzymology
  • nonribosomal peptide synthesis
  • tyrocidine antibiotics
  • Bacillus
  • Catalytic Domain
  • Crystallography, X-Ray
  • Glutamic Acid
  • Models, Molecular
  • Peptide Synthases
  • Protein Structure, Tertiary
Sprache
eng
Country
United States
Paginierung
1442 - 1452
PII
S1399004714004398
Datum der Veröffentlichung
2014
Status
Published
Datum, an dem der Datensatz öffentlich gemacht wurde
2015
Titel
Structure of the epimerization domain of tyrocidine synthetase A.
Sub types
  • Journal Article
  • Research Support, Non-U.S. Gov't
Ausgabe der Zeitschrift
70

Data source: PubMed

Beziehungen:
Property of

Tools