Sandbox Reserved 982: Difference between revisions

Line 7:

Shiga toxin (stx) has multiple classifications. The shiga toxin produced by ''Shigella dysenteriae'' is classified as stx, while shiga toxin produced by Escherichia coli is classified as either stx1 or stx2. All three classifications vary slightly in structure but have identical functions. The A sub-unit of stx1 differs from stx by one residue: a serine in position 45 as opposed to threonine<ref name="Fraser">Fraser, M. E., Fujinaga, M., Cherney, M. M., Melton-Celsa, A. R., Twiddy, E. M., O’Brien, A. D., & James, M. N. G. (2004). Structure of shiga toxin type 2 (Stx2) from Escherichia coli O157:H7. The Journal of Biological Chemistry, 279(26), 27511–27517. doi:10.1074/jbc.M401939200</ref>.

Stx is a 70 kDa AB5 protein, meaning that it is composed of an A sub-unit bound to a B pentamer. A ~~noncovalent interaction causes the association between the A and~~ B sub-units~~, as~~ the carboxy ~~terminal~~ tail of the A sub-unit ~~is surrounded~~ by ~~the B pentamer~~. <scene name='68/687332/Sub-unit_a/2'>The A sub-unit</scene> is 293 amino acids long with its active site being <scene name='68/687332/Active_site_for_stx/1'>glutamic acid 167 (1R4Q)</scene>. Though the active site contains a single residue, studies have shown that the first 239 residues are essential for the enzymatic activity of the A sub-unit. Residues 240-251 are essential for the A sub-unit’s translocation from the endoplasmic reticulum of an infected cell to the cytosol<ref name="Sandvig">Sandvig, K., & van Deurs, B. (2000). Entry of ricin and Shiga toxin into cells: molecular mechanisms and medical perspectives. The EMBO Journal, 19(22), 5943–5950. doi:10.1093/emboj/19.22.5943</ref>.

Stx is a 70 kDa AB5 protein, meaning that it is composed of an A sub-unit bound to a B pentamer. A pentamer of B sub-units encircles the carboxy tail of the A sub-unit stabilized by a series of non-covalent interactions. <scene name='68/687332/Sub-unit_a/2'>The A sub-unit</scene> is 293 amino acids long with its active site being <scene name='68/687332/Active_site_for_stx/1'>glutamic acid 167 (1R4Q)</scene>. Though the active site contains a single residue, studies have shown that the first 239 residues are essential for the enzymatic activity of the A sub-unit. Residues 240-251 are essential for the A sub-unit’s translocation from the endoplasmic reticulum of an infected cell to the cytosol<ref name="Sandvig">Sandvig, K., & van Deurs, B. (2000). Entry of ricin and Shiga toxin into cells: molecular mechanisms and medical perspectives. The EMBO Journal, 19(22), 5943–5950. doi:10.1093/emboj/19.22.5943</ref>.

The A sub-unit can be broken down into A1 and A2 units. This break down occurs when a trypsin sensitive region, residues 248-251, is cleaved. This cleavage results in the only remaining link being a <scene name='68/687332/Disulfide_bridge/1'>disulfide bridge (1R4Q)</scene> between cysteine 242 and cysteine 261. If the disulfide bridge is reduced, the A1 and A2 fragments can completely separate. Interestingly, the disulfide bridge blocks the active site of the A sub-unit, so the A sub-unit is not enzymatically active unless it has been cleaved<ref name ="Fraser">Fraser, M. E., Fujinaga, M., Cherney, M. M., Melton-Celsa, A. R., Twiddy, E. M., O’Brien, A. D., & James, M. N. G. (2004). Structure of shiga toxin type 2 (Stx2) from Escherichia coli O157:H7. The Journal of Biological Chemistry, 279(26), 27511–27517. doi:10.1074/jbc.M401939200</ref>.

Sandbox Reserved 982: Difference between revisions

Navigation menu

Page actions

Page actions

Personal tools

Navigation

Search

Tools

@@ Line 7: / Line 7: @@
 Shiga toxin (stx) has multiple classifications. The shiga toxin produced by ''Shigella dysenteriae'' is classified as stx, while shiga toxin produced by Escherichia coli is classified as either stx1 or stx2. All three classifications vary slightly in structure but have identical functions. The A sub-unit of stx1 differs from stx by one residue: a serine in position 45 as opposed to threonine<ref name="Fraser">Fraser, M. E., Fujinaga, M., Cherney, M. M., Melton-Celsa, A. R., Twiddy, E. M., O’Brien, A. D., & James, M. N. G. (2004). Structure of shiga toxin type 2 (Stx2) from Escherichia coli O157:H7. The Journal of Biological Chemistry, 279(26), 27511–27517. doi:10.1074/jbc.M401939200</ref>.
-Stx is a 70 kDa AB5 protein, meaning that it is composed of an A sub-unit bound to a B pentamer. A noncovalent interaction causes the association between the A and B sub-units, as the carboxy terminal tail of the A sub-unit is surrounded by the B pentamer. <scene name='68/687332/Sub-unit_a/2'>The A sub-unit</scene> is 293 amino acids long with its active site being <scene name='68/687332/Active_site_for_stx/1'>glutamic acid 167 (1R4Q)</scene>. Though the active site contains a single residue, studies have shown that the first 239 residues are essential for the enzymatic activity of the A sub-unit. Residues 240-251 are essential for the A sub-unit’s translocation from the endoplasmic reticulum of an infected cell to the cytosol<ref name="Sandvig">Sandvig, K., & van Deurs, B. (2000). Entry of ricin and Shiga toxin into cells: molecular mechanisms and medical perspectives. The EMBO Journal, 19(22), 5943–5950. doi:10.1093/emboj/19.22.5943</ref>.
+Stx is a 70 kDa AB5 protein, meaning that it is composed of an A sub-unit bound to a B pentamer. A pentamer of B sub-units encircles the carboxy tail of the A sub-unit stabilized by a series of non-covalent interactions. <scene name='68/687332/Sub-unit_a/2'>The A sub-unit</scene> is 293 amino acids long with its active site being <scene name='68/687332/Active_site_for_stx/1'>glutamic acid 167 (1R4Q)</scene>. Though the active site contains a single residue, studies have shown that the first 239 residues are essential for the enzymatic activity of the A sub-unit. Residues 240-251 are essential for the A sub-unit’s translocation from the endoplasmic reticulum of an infected cell to the cytosol<ref name="Sandvig">Sandvig, K., & van Deurs, B. (2000). Entry of ricin and Shiga toxin into cells: molecular mechanisms and medical perspectives. The EMBO Journal, 19(22), 5943–5950. doi:10.1093/emboj/19.22.5943</ref>.
 The A sub-unit can be broken down into A1 and A2 units. This break down occurs when a trypsin sensitive region, residues 248-251, is cleaved. This cleavage results in the only remaining link being a <scene name='68/687332/Disulfide_bridge/1'>disulfide bridge (1R4Q)</scene> between cysteine 242 and cysteine 261. If the disulfide bridge is reduced, the A1 and A2 fragments can completely separate. Interestingly, the disulfide bridge blocks the active site of the A sub-unit, so the A sub-unit is not enzymatically active unless it has been cleaved<ref name ="Fraser">Fraser, M. E., Fujinaga, M., Cherney, M. M., Melton-Celsa, A. R., Twiddy, E. M., O’Brien, A. D., & James, M. N. G. (2004). Structure of shiga toxin type 2 (Stx2) from Escherichia coli O157:H7. The Journal of Biological Chemistry, 279(26), 27511–27517. doi:10.1074/jbc.M401939200</ref>.