Physical Sciences and Mathematics | Open Access Articles

Plp And Gaba Trigger Gabr-Mediated Transcription Regulation In Bacillus Subtilis Via External Aldimine Formation, Rui Wu, Ruslan Sanishvili, Boris R. Belitsky, Jose I. Juncosa, Hoang V. Le, Helaina J. S. Lehrer, Michael Farley, Richard B. Silverman, Gregory A. Petsko, Dagmar Ringe, Dali Liu

Chemistry: Faculty Publications and Other Works

The Bacillus subtilis protein regulator of the gabTD operon and its own gene (GabR) is a transcriptional activator that regulates transcription of γ-aminobutyric acid aminotransferase (GABA-AT; GabT) upon interactions with pyridoxal-5′-phosphate (PLP) and GABA, and thereby promotes the biosynthesis of glutamate from GABA. We show here that the external aldimine formed between PLP and GABA is apparently responsible for triggering the GabR-mediated transcription activation. Details of the “active site” in the structure of the GabR effector-binding/oligomerization (Eb/O) domain suggest that binding a monocarboxylic γ-amino acid such as GABA should be preferred over dicarboxylic acid ligands. A reactive GABA analog, ( …

Go to article

Binding Of Transcription Factor Gabr To Dna Requires Recognition Of Dna Shape At A Location Distinct From Its Cognate Binding Site, Dali Liu, Walid A. Al-Zyoud, Robert Mg. Hynson, Lorraine A. Ganuelas, Adelle Cf. Coster, Anthony P. Duff, Matthew Ab. Baker, Alastair G. Stewart, Eleni Giannoulatou, Joshua Wk> Ho, Katharina Gaus, Lawrence K. Lee, Till Böcking

Chemistry: Faculty Publications and Other Works

Mechanisms for transcription factor recognition of specific DNA base sequences are well characterized and recent studies demonstrate that the shape of these cognate binding sites is also important. Here, we uncover a new mechanism where the transcription factor GabR simultaneously recognizes two cognate binding sites and the shape of a 29 bp DNA sequence that bridges these sites. Small-angle X-ray scattering and multi-angle laser light scattering are consistent with a model where the DNA undergoes a conformational change to bend around GabR during binding. In silico predictions suggest that the bridging DNA sequence is likely to be bendable in one …

Go to article

Crystal Structure Of Bacillus Subtilis Gabr, An Autorepressor And Transcriptional Activator Of Gabt, Raji Edayathumangalam, Rui Wu, Roman Garcia, Yuguang Wang, Wei Wang

Chemistry: Faculty Publications and Other Works

Bacillus subtilis GabR is a transcription factor that regulates gamma-aminobutyric acid (GABA) metabolism. GabR is a member of the understudied MocR/GabR subfamily of the GntR family of transcription regulators. A typical MocR/GabR-type regulator is a chimeric protein containing a short N-terminal helix-turn-helix DNA-binding domain and a long C-terminal pyridoxal 5′-phosphate (PLP)-binding putative aminotransferase domain. In the presence of PLP and GABA, GabR activates the gabTD operon, which allows the bacterium to use GABA as nitrogen and carbon sources. GabR binds to its own promoter and represses gabRtranscription in the absence of GABA. Here, we report two crystal structures of …

Go to article

Physical Sciences and Mathematics Commons^™

Full-Text Articles in Physical Sciences and Mathematics

Plp And Gaba Trigger Gabr-Mediated Transcription Regulation In Bacillus Subtilis Via External Aldimine Formation, Rui Wu, Ruslan Sanishvili, Boris R. Belitsky, Jose I. Juncosa, Hoang V. Le, Helaina J. S. Lehrer, Michael Farley, Richard B. Silverman, Gregory A. Petsko, Dagmar Ringe, Dali Liu

Chemistry: Faculty Publications and Other Works

Chemistry: Faculty Publications and Other Works

Crystal Structure Of Bacillus Subtilis Gabr, An Autorepressor And Transcriptional Activator Of Gabt, Raji Edayathumangalam, Rui Wu, Roman Garcia, Yuguang Wang, Wei Wang

Chemistry: Faculty Publications and Other Works