GLUT1: Difference between revisions

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<scene name='91/910668/Glut1_default_view_charged/1'>GLUT1</scene> has a <scene name='91/910668/Glut1_hydrophobic_pocket/1'>hydrophobic pocket</scene> and is proposed to be comprised of <scene name='91/910668/Glut1_hps_2/1'>six amino acids</scene><scene name='91/910668/Glut1_hps_2/5'>(view 2)</scene>. In the structure [[4pyp]], these residues are Gly27, Thr30, Ile164, Val165, Ile168, and Phe291. This hydrophobic pocket has been proposed to facilitate substrate binding and unbinding between the "occluded" and "inward-open" conformations.<ref>PMID:27128978</ref> In this crystal structure, <scene name='91/910668/B-ng_in_4pyp/1'>N-nonyl-β-D-glucopyranoside (β-NG)</scene> acts as a glucose analog that binds the hydrophobic pocket.<ref>PMID:24847886</ref>

The GLUT1 transporter also has three proposed ATP-binding sites. The lone <scene name='91/910668/Glut1_atp_binding_1/3'>extracellular ATP-binding site</scene> is proposed to be comprised of the residues Gly111, Phe112, Ser113, Lys114, Leu115, Gly116, Lys117, and Ser118. This is a domain consistent with Walker Motif A (G-X-X-G/X-X-G-K-T/X). The <scene name='91/910668/Glut1_atp_binding_2/3'>second ATP-binding site</scene> is one of two in the cytoplasmic portion of the protein. The residues comprising this ATP-binding site are Lys225, Ser226, Val227, Leu228, and Lys229. The <scene name='91/910668/Atp_binding_site_3/4'>third ATP-binding site</scene>, also localized to the cytoplasm, is comprised of the amino acids Gly332, Arg 333, Arg334, Thr335, Leu336, His337, and Leu338. This sequence is consistent with Walker Motif B (G-X-X-X-L-X-X).<ref>PMID:11425315</ref> As mentioned earlier in the page, both Walker motifs A and B are highly conserved. Some studies on GLUT1 show that ATP binding to the cytosolic domains causes C-terminus binding to the C-terminal side of the intracellular loop of the protein, preventing substrate import. ATP binding is not known to have any effects when binding extracellularly.<ref>PMID:25715702</ref>

The GLUT1 transporter also has three proposed ATP-binding sites. The lone <scene name='91/910668/Glut1_atp_binding_1/3'>extracellular ATP-binding site</scene> is proposed to be comprised of the residues Gly111, Phe112, Ser113, Lys114, Leu115, Gly116, Lys117, and Ser118. This is a domain consistent with Walker Motif A (G-X-X-G/X-X-G-K-T/X). The <scene name='91/910668/Glut1_atp_binding_2/3'>second ATP-binding site</scene> is one of two in the cytoplasmic portion of the protein. The residues comprising this ATP-binding site are Lys225, Ser226, Val227, Leu228, and Lys229. The <scene name='91/910668/Atp_binding_site_3/5'>third ATP-binding site</scene>, also localized to the cytoplasm, is comprised of the amino acids Gly332, Arg 333, Arg334, Thr335, Leu336, His337, and Leu338. This sequence is consistent with Walker Motif B (G-X-X-X-L-X-X).<ref>PMID:11425315</ref> As mentioned earlier in the page, both Walker motifs A and B are highly conserved. Some studies on GLUT1 show that ATP binding to the cytosolic domains causes C-terminus binding to the C-terminal side of the intracellular loop of the protein, preventing substrate import. ATP binding is not known to have any effects when binding extracellularly.<ref>PMID:25715702</ref>

Several types of GLUT1 inhibitors exist, one being [https://en.wikipedia.org/wiki/Cytochalasin_B cytochalasin b]. Two Trp residues, Trp388 and Trp412, are thought to play a major role in <scene name='91/910668/Glut1_cytochalasin_b_1/1'>cytochalasin b binding to GLUT1</scene> via hydrophobic interactions.<ref>PMID:7078104</ref>

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@@ Line 46: / Line 46: @@
 <scene name='91/910668/Glut1_default_view_charged/1'>GLUT1</scene> has a <scene name='91/910668/Glut1_hydrophobic_pocket/1'>hydrophobic pocket</scene> and is proposed to be comprised of <scene name='91/910668/Glut1_hps_2/1'>six amino acids</scene><scene name='91/910668/Glut1_hps_2/5'>(view 2)</scene>. In the structure [[4pyp]], these residues are Gly27, Thr30, Ile164, Val165, Ile168, and Phe291. This hydrophobic pocket has been proposed to facilitate substrate binding and unbinding between the "occluded" and "inward-open" conformations.<ref>PMID:27128978</ref> In this crystal structure, <scene name='91/910668/B-ng_in_4pyp/1'>N-nonyl-β-D-glucopyranoside (β-NG)</scene> acts as a glucose analog that binds the hydrophobic pocket.<ref>PMID:24847886</ref>
-The GLUT1 transporter also has three proposed ATP-binding sites. The lone <scene name='91/910668/Glut1_atp_binding_1/3'>extracellular ATP-binding site</scene> is proposed to be comprised of the residues Gly111, Phe112, Ser113, Lys114, Leu115, Gly116, Lys117, and Ser118. This is a domain consistent with Walker Motif A (G-X-X-G/X-X-G-K-T/X). The <scene name='91/910668/Glut1_atp_binding_2/3'>second ATP-binding site</scene> is one of two in the cytoplasmic portion of the protein. The residues comprising this ATP-binding site are Lys225, Ser226, Val227, Leu228, and Lys229. The <scene name='91/910668/Atp_binding_site_3/4'>third ATP-binding site</scene>, also localized to the cytoplasm, is comprised of the amino acids Gly332, Arg 333, Arg334, Thr335, Leu336, His337, and Leu338. This sequence is consistent with Walker Motif B (G-X-X-X-L-X-X).<ref>PMID:11425315</ref> As mentioned earlier in the page, both Walker motifs A and B are highly conserved. Some studies on GLUT1 show that ATP binding to the cytosolic domains causes C-terminus binding to the C-terminal side of the intracellular loop of the protein, preventing substrate import. ATP binding is not known to have any effects when binding extracellularly.<ref>PMID:25715702</ref>
+The GLUT1 transporter also has three proposed ATP-binding sites. The lone <scene name='91/910668/Glut1_atp_binding_1/3'>extracellular ATP-binding site</scene> is proposed to be comprised of the residues Gly111, Phe112, Ser113, Lys114, Leu115, Gly116, Lys117, and Ser118. This is a domain consistent with Walker Motif A (G-X-X-G/X-X-G-K-T/X). The <scene name='91/910668/Glut1_atp_binding_2/3'>second ATP-binding site</scene> is one of two in the cytoplasmic portion of the protein. The residues comprising this ATP-binding site are Lys225, Ser226, Val227, Leu228, and Lys229. The <scene name='91/910668/Atp_binding_site_3/5'>third ATP-binding site</scene>, also localized to the cytoplasm, is comprised of the amino acids Gly332, Arg 333, Arg334, Thr335, Leu336, His337, and Leu338. This sequence is consistent with Walker Motif B (G-X-X-X-L-X-X).<ref>PMID:11425315</ref> As mentioned earlier in the page, both Walker motifs A and B are highly conserved. Some studies on GLUT1 show that ATP binding to the cytosolic domains causes C-terminus binding to the C-terminal side of the intracellular loop of the protein, preventing substrate import. ATP binding is not known to have any effects when binding extracellularly.<ref>PMID:25715702</ref>
 Several types of GLUT1 inhibitors exist, one being [https://en.wikipedia.org/wiki/Cytochalasin_B cytochalasin b]. Two Trp residues, Trp388 and Trp412, are thought to play a major role in <scene name='91/910668/Glut1_cytochalasin_b_1/1'>cytochalasin b binding to GLUT1</scene> via hydrophobic interactions.<ref>PMID:7078104</ref>