ToxT: Difference between revisions
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<u>Ligand-binding</u>. <scene name='ToxT_Transcriptional_Regulator_in_Vibrio_cholerae/Barrel/1'>A nine-stranded beta sheet sandwich</scene> or "jelly-roll" with three other alpha helices (overall making up the <scene name='ToxT_Transcriptional_Regulator_in_Vibrio_cholerae/N-terminus/1'>N-terminus</scene>) contain a <scene name='ToxT_Transcriptional_Regulator_in_Vibrio_cholerae/Binding_pocket/1'>binding pocket</scene>. This is | <u>Ligand-binding</u>. <scene name='ToxT_Transcriptional_Regulator_in_Vibrio_cholerae/Barrel/1'>A nine-stranded beta sheet sandwich</scene> or "jelly-roll" with three other alpha helices (overall making up the <scene name='ToxT_Transcriptional_Regulator_in_Vibrio_cholerae/N-terminus/1'>N-terminus</scene>) contain a <scene name='ToxT_Transcriptional_Regulator_in_Vibrio_cholerae/Binding_pocket/1'>binding pocket</scene>. This is made from several residues from the N-terminus (Y12, Y20, F22, L25, I27, K31, F33, L61, F69, L71, V81, and V83), and a few from the C-terminus (I226, K230, M259, V261, Y266, and M269). The pocket is highly hydrophobic, and has a known volume of 780.9 Angstroms.<ref name="structure">PMID: 20133655</ref> This pocket contains a ligand: <scene name='ToxT_Transcriptional_Regulator_in_Vibrio_cholerae/Binding_pocket/2'>cis-palmitoleate</scene> <ref name="structure">PMID: 20133655</ref> which appears to have a negative effect on virulence when present in vitro. The <i>cis</i>-palmitoleate forms <scene name='ToxT_Transcriptional_Regulator_in_Vibrio_cholerae/Salt_bridges_pam/1'>salt bridges</scene> with residues K31 and K230 (for detail, see Figure 1B of: [http://www.pnas.org/content/107/7/2860/F1.expansion.html]). This unsaturated fatty acid, like other UFAs,[http://en.wikipedia.org/wiki/Fatty_acid#Unsaturated_fatty_acids] tend to inhibit genes under the control of ToxT. The | ||
Specifically, the <i>cis</i>-palmitoleate appears to bind directly to ToxT, change its conformation, and thus lower the ability to bind DNA and form dimers.<ref name="structure">PMID: 20133655</ref> The presence of UFAs is associated with being in the lumen of the intestine during the bacterial infection. Here, binding of PAM brings K31 and K230 together and essentially closes off ToxT. K230 is at the end of helix seven, and binding to K31 causes pulling helix six into an unfavorable conformation that disallows DNA binding. In lower concentration of fatty acids, ie: after penetrating the intestine's mucus, the two lysine residues repel each other and give ToxT an open conformation by giving helix seven and thus six freedom, allowing DNA binding.<ref name="structure">PMID: 20133655</ref> | Specifically, the <i>cis</i>-palmitoleate appears to bind directly to ToxT, change its conformation, and thus lower the ability to bind DNA and form dimers.<ref name="structure">PMID: 20133655</ref> The presence of UFAs is associated with being in the lumen of the intestine during the bacterial infection. Here, binding of PAM brings K31 and K230 together and essentially closes off ToxT. K230 is at the end of helix seven, and binding to K31 causes pulling helix six into an unfavorable conformation that disallows DNA binding. In lower concentration of fatty acids, ie: after penetrating the intestine's mucus, the two lysine residues repel each other and give ToxT an open conformation by giving helix seven and thus six freedom, allowing DNA binding.<ref name="structure">PMID: 20133655</ref> | ||
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