Back to Search
Start Over
Structural Insights into a Flavin-Dependent [4 + 2] Cyclase that Catalyzes trans-Decalin Formation in Pyrroindomycin Biosynthesis
- Source :
- Cell chemical biology. 25(6)
- Publication Year :
- 2017
-
Abstract
- Summary Here, we provide structural insights into PyrE3, a flavin-dependent [4 + 2] cyclase that catalyzes trans -decalin formation in the biosynthesis of pyrroindomycins. PyrE3 shares an architecture/domain organization head-to-tail similarity with the members of the family of para -hydroxybenzoate hydroxylase (pHBH)-fold monooxygenases, and possesses a flavin adenine dinucleotide (FAD)-binding domain, a middle domain, and a C-terminal thioredoxin-like domain. The FAD-binding domain forms a central hub of the protein structure, and binds with FAD in a "closed" conformation of pHBH-fold family monooxygenases known for their highly dynamic catalytic processes. FAD plays an essential structural role in PyrE3, where it is amenable to redox change; however, redox change has little effect on [4 + 2] cyclization activity. PyrE3 appears to selectively accommodate a tetramate-containing, linear polyene intermediate in a highly positively charged pocket, which is located at the interface between the FAD-binding domain and the middle domain, and can accelerate trans -decalin formation likely through an endo -selective [4 + 2] transition state.
- Subjects :
- Models, Molecular
Stereochemistry
Dinitrocresols
Clinical Biochemistry
Flavin group
Biology
Naphthalenes
010402 general chemistry
Crystallography, X-Ray
01 natural sciences
Biochemistry
Cyclase
Mixed Function Oxygenases
chemistry.chemical_compound
Protein structure
Decalin
Oxidoreductase
Drug Discovery
Molecular Biology
Pharmacology
chemistry.chemical_classification
Flavin adenine dinucleotide
Molecular Structure
010405 organic chemistry
Polyene
0104 chemical sciences
chemistry
Hydroxybenzoate
Biocatalysis
Molecular Medicine
Macrolides
Subjects
Details
- ISSN :
- 24519448
- Volume :
- 25
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- Cell chemical biology
- Accession number :
- edsair.doi.dedup.....185e1d6ffb5cd2c700abfa8b51cd892b