Linked Life Data

21417270

Source:http://linkedlifedata.com/resource/pubmed/id/21417270

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
14
pubmed:dateCreated
2011-4-6
pubmed:abstractText
Pacidamycins are a family of uridyl peptide antibiotics that inhibit the translocase MraY, an essential enzyme in bacterial cell wall biosynthesis that to date has not been clinically targeted. The pacidamycin structural skeleton contains a doubly inverted peptidyl chain with a ?-peptide and a ureido linkage as well as a 3'-deoxyuridine nucleoside attached to DABA(3) of the peptidyl chain via an enamide linkage. Although the biosynthetic gene cluster for pacidamycins was identified recently, the assembly line of this group of peptidyl nucleoside antibiotics remained poorly understood because of the highly dissociated nature of the encoded nonribosomal peptide synthetase (NRPS) domains and modules. This work has identified a minimum set of enzymes needed for generation of the pacidamycin scaffold from amino acid and nucleoside monomers, highlighting a freestanding thiolation (T) domain (PacH) as a key carrier component in the peptidyl chain assembly as well as a freestanding condensation (C) domain (PacI) catalyzing the release of the assembled peptide by a nucleoside moiety. On the basis of the substrate promiscuity of this enzymatic assembly line, several pacidamycin analogues were produced using in vitro total biosynthesis.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1520-5126
pubmed:author
pubmed:copyrightInfo
© 2011 American Chemical Society
pubmed:issnType
Electronic
pubmed:day
13
pubmed:volume
133
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5240-3
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Nine enzymes are required for assembly of the pacidamycin group of peptidyl nucleoside antibiotics.
pubmed:affiliation
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural