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PMID: 22844465 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Structure of an MmyB-like regulator from C. aurantiacus, member of a new transcription factor family linked to antibiotic metabolism in actinomycetes.

PloS one ·Vol. 7 ·No. 7 ·2012-00-00 ·Pages e41359

Xu Q, van Wezel GP, Chiu HJ, Jaroszewski L, Klock HE, Knuth MW, Miller MD, Lesley SA, Godzik A, Elsliger MA, Deacon AM, Wilson IA

Abstract

Actinomycetes are important bacterial sources of antibiotics and other secondary metabolites. Many antibiotic gene clusters are controlled by pathway-specific activators that act in response to growth conditions. Here we present the crystal structure of an MmyB-like transcription regulator MltR (PDB code 3pxp) (Caur_2278) from Chloroflexus aurantiacus, in complex with a fatty acid (myristic acid). MltR is a distant homolog of the methylenomycin activator MmyB and consists of an Xre-type N-terminal DNA-binding domain and a C-terminal ligand-binding module that is related to the Per-Arnt-Sim (PAS) domain. This structure has enabled identification of a new family of bacterial transcription factors that are distributed predominantly in actinomycetes. Bioinformatics analysis of MltR and other characterized family members suggest that they are likely associated with antibiotic and fatty acid metabolism in actinomycetes. Streptomyces coelicolor SCO4944 is a candidate as an ancestral member of the family. Its ortholog in S. griseus, SGR_6891, is induced by A-factor, a γ-butyrolactone that controls antibiotic production and development, and is adjacent to the A-factor synthase gen, afsA. The location of mltR/mmyB homologs, in particular those adjacent to less well-studied antibiotic-related genes, makes them interesting genetic markers for identifying new antibiotic genes. A model for signal-triggered DNA-binding by MltR is proposed.

MeSH Terms
Actinomyces/metabolism Amino Acid Sequence Anti-Bacterial Agents/metabolism Bacterial Proteins/chemistry,metabolism Chloroflexus Crystallography, X-Ray DNA, Bacterial/metabolism Ligands Models, Molecular Molecular Sequence Data Myristic Acid/metabolism Protein Multimerization Protein Structure, Quaternary Protein Structure, Tertiary Transcription Factors/chemistry,metabolism
Chemicals
Anti-Bacterial Agents Bacterial Proteins DNA, Bacterial Ligands Transcription Factors Myristic Acid
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Xu Qingping
Joint Center for Structural Genomics, La Jolla, California, United States of America.
van Wezel Gilles P
Chiu Hsiu-Ju
Jaroszewski Lukasz
Klock Heath E
Knuth Mark W
Miller Mitchell D
Lesley Scott A
Godzik Adam
Elsliger Marc-André
Deacon Ashley M
Wilson Ian A
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Article Info
Journal
PloS one
Abbr.
PLoS One
ISSN
1932-6203
DOI
10.1371/journal.pone.0041359
Published
2012-00-00
Epub
2012-00-26
Pages
e41359
Language
English
Region
United States
NLM ID
101285081
PMCID
PMC3406030
Subset
IM
Grants
NCRR NIH HHS · P41RR001209 · United States
NIGMS NIH HHS · U54 GM094586 · United States
NCRR NIH HHS · P41 RR001209 · United States
NIGMS NIH HHS · P41GM103393 · United States
NIGMS NIH HHS · U54 GM074898 · United States
NIGMS NIH HHS · P41 GM103393 · United States
NIAID NIH HHS · P01 AI058113 · United States
NIGMS NIH HHS · GM074898 · United States
Databases
PDB
3PXP
Corrections
ErratumIn
-
External Links
PubMed source DOI: 10.1371/journal.pone.0041359 PMC Full Text View journal details
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