Sandbox Reserved 1613: Difference between revisions

Line 6:

The ABCG2 protein is comprised of a homodimer which each have two specific domains: one spanning the cell membrane and one involved with nucleotide binding.

===Transmembrane Domains===

In the transmembrane domain is located the leucine plug that separates the first site of binding from the second site of binding for the substrate. This is only opened when the protein is shifted from its interior facing to exterior facing formation by the transfer of a phosphate off of an ATP. This causes a shift and transfer to the second binding site which is open to the extracellular matrix. The Fab-5D3 antigen binding fragment was found to stabilize the protein in its inward facing conformation which allowed for high resolution images of the protein to be taken in this conformation. Without Fab attached, the conformation of the protein was constantly in flux, transporting substrates out of the cell constantly. Fab was found to only stabilize ABCG2 on the extracellular side. Three important interactions between Fab fragments and ABCG2 were important to binding stability and favorability. This binding occurred at the <scene name='83/832939/El-3/1'>EL-3</scene> of ABCG2 which is the helices that stretches the furthest from the cell membrane. These interactions were two disulfide bonds, one intramolecularly and the other intermolecularly, and an n-glycosylation site at residue Asn-596.

In the transmembrane domain is located the leucine plug that separates the first site of binding from the second site of binding for the substrate. This is only opened when the protein is shifted from its interior facing to exterior facing formation by the transfer of a phosphate off of an ATP. This causes a shift and transfer to the second binding site which is open to the extracellular matrix. The Fab-5D3 antigen binding fragment was found to stabilize the protein in its inward facing conformation which allowed for high resolution images of the protein to be taken in this conformation. Without Fab attached, the conformation of the protein was constantly in flux, transporting substrates out of the cell constantly. Fab was found to only stabilize ABCG2 on the extracellular side. Three important interactions between Fab fragments and ABCG2 were important to binding stability and favorability. This binding occurred at the <scene name='83/832939/El-3/1'>EL-3</scene> of ABCG2 which is the helices that stretches the furthest from the cell membrane. These interactions were two disulfide bonds, one intramolecularly and the other intermolecularly, and an n-<scene name='83/832939/Glycos_site/1'>glycosylation site</scene> at residue Asn-596.

===Nucleotide Binding Domains===

These two domains contain the active site of this transporter protein. The interest in this protein is in its involvement with mutidrug resistant cancer cells. This involvement is due to its active site's promiscuity as many xenobiotics have been found to transported to the outside of the cell by this transporter.

Sandbox Reserved 1613: Difference between revisions

Navigation menu

Page actions

Page actions

Personal tools

Navigation

Search

Tools

@@ Line 6: / Line 6: @@
 The ABCG2 protein is comprised of a homodimer which each have two specific domains: one spanning the cell membrane and one involved with nucleotide binding.
 ===Transmembrane Domains===
-In the transmembrane domain is located the leucine plug that separates the first site of binding from the second site of binding for the substrate. This is only opened when the protein is shifted from its interior facing to exterior facing formation by the transfer of a phosphate off of an ATP. This causes a shift and transfer to the second binding site which is open to the extracellular matrix. The Fab-5D3 antigen binding fragment was found to stabilize the protein in its inward facing conformation which allowed for high resolution images of the protein to be taken in this conformation. Without Fab attached, the conformation of the protein was constantly in flux, transporting substrates out of the cell constantly. Fab was found to only stabilize ABCG2 on the extracellular side. Three important interactions between Fab fragments and ABCG2 were important to binding stability and favorability. This binding occurred at the <scene name='83/832939/El-3/1'>EL-3</scene> of ABCG2 which is the helices that stretches the furthest from the cell membrane. These interactions were two disulfide bonds, one intramolecularly and the other intermolecularly, and an n-glycosylation site at residue Asn-596.
+In the transmembrane domain is located the leucine plug that separates the first site of binding from the second site of binding for the substrate. This is only opened when the protein is shifted from its interior facing to exterior facing formation by the transfer of a phosphate off of an ATP. This causes a shift and transfer to the second binding site which is open to the extracellular matrix. The Fab-5D3 antigen binding fragment was found to stabilize the protein in its inward facing conformation which allowed for high resolution images of the protein to be taken in this conformation. Without Fab attached, the conformation of the protein was constantly in flux, transporting substrates out of the cell constantly. Fab was found to only stabilize ABCG2 on the extracellular side. Three important interactions between Fab fragments and ABCG2 were important to binding stability and favorability. This binding occurred at the <scene name='83/832939/El-3/1'>EL-3</scene> of ABCG2 which is the helices that stretches the furthest from the cell membrane. These interactions were two disulfide bonds, one intramolecularly and the other intermolecularly, and an n-<scene name='83/832939/Glycos_site/1'>glycosylation site</scene> at residue Asn-596.
 ===Nucleotide Binding Domains===
 These two domains contain the active site of this transporter protein. The interest in this protein is in its involvement with mutidrug resistant cancer cells. This involvement is due to its active site's promiscuity as many xenobiotics have been found to transported to the outside of the cell by this transporter.