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Molecular Basis of BioJ, a Unique Gatekeeper in Bacterial Biotin Synthesis
- Source :
- iScience, iScience, Vol 19, Iss, Pp 796-808 (2019)
- Publication Year :
- 2019
- Publisher :
- Elsevier BV, 2019.
-
Abstract
- Summary Biotin is an indispensable cofactor in the three domains of life. The unusual virulence factor BioJ of Francisella catalyzes the formation of pimeloyl-ACP, an intermediate in biotin synthesis. Here, we report the 1.58 Å crystal structure of BioJ, the enzymatic activity of which is determined with the in vitro reconstituted reaction and biotin bioassay in vivo. Unlike the paradigm BioH, BioJ displays an atypical α/β-hydrolase fold. A structurally conserved catalytic triad (S151, D248, and H278) of BioJ is functionally defined. A proposed model for BioJ catalysis involves two basic residues-rich cavities, of which cavity-1, rather than cavity-2, binds to the ACP moiety of its physiological substrate, pimeloyl-ACP methyl ester. In summary, this finding provides molecular insights into the BioJ gatekeeper of biotin synthesis.<br />Graphical Abstract<br />Highlights • BioJ is a distinct gatekeeper of biotin synthesis • We report structural and functional definition of BioJ • We propose a working model for BioJ-substrate binding in addition to catalytic triad • It furthers our understanding how the substrate is gatekept by BioJ in biotin synthesis<br />Biological Sciences; Microbiology; Structural Biology
- Subjects :
- 0301 basic medicine
02 engineering and technology
Microbiology
Article
Virulence factor
Cofactor
03 medical and health sciences
chemistry.chemical_compound
Biotin
Structural Biology
Catalytic triad
Moiety
lcsh:Science
chemistry.chemical_classification
Multidisciplinary
biology
Biological Sciences
021001 nanoscience & nanotechnology
biology.organism_classification
030104 developmental biology
Enzyme
chemistry
Structural biology
Biochemistry
biology.protein
Francisella
lcsh:Q
0210 nano-technology
Subjects
Details
- ISSN :
- 25890042
- Volume :
- 19
- Database :
- OpenAIRE
- Journal :
- iScience
- Accession number :
- edsair.doi.dedup.....897a51fd497740da6df9ff36a5dc4de1