HOAT1: Difference between revisions

Line 81:

'''Key Structural Characteristics:'''

*'''Overall Fold:'''

::*Adopts the classic Major Facilitator Superfamily (MFS) fold.

:*Adopts the classic Major Facilitator Superfamily (MFS) fold.

::*Comprises 12 transmembrane helices (TMs 1-12).

:*Comprises 12 transmembrane helices (TMs 1-12).

::*Exhibits pseudo-two-fold symmetry, divided into an N-lobe (TMs 1-6) and a C-lobe (TMs 7-12).

:*Exhibits pseudo-two-fold symmetry, divided into an N-lobe (TMs 1-6) and a C-lobe (TMs 7-12).

*'''Central Binding Cavity:'''

::*The cavity is located between the N-lobe (formed by TM1, TM2, TM4, TM5) and the C-lobe (formed by TM7, TM8, TM10, TM11).

:*The cavity is located between the N-lobe (formed by TM1, TM2, TM4, TM5) and the C-lobe (formed by TM7, TM8, TM10, TM11).

::*It possesses a positively charged electrostatic environment, which explains its strong preference for transporting anionic substrates.

:*It possesses a positively charged electrostatic environment, which explains its strong preference for transporting anionic substrates.

::*The cavity is lined by 29 residues, forming a hydrophobic and aromatic-rich environment.

:*The cavity is lined by 29 residues, forming a hydrophobic and aromatic-rich environment.

*'''Cavity Borders and Cytosolic Gate:'''

::*The top border (extracellular side) of the cavity is formed by residues including N35, Y230, Y353, and Y354 and are involved in substrate recognition

:*The top border (extracellular side) of the cavity is formed by residues including N35, Y230, Y353, and Y354 and are involved in substrate recognition

::*The bottom border (cytosolic side) features a narrow "thin bottom gate" formed by residues M207 and F442. The interaction between these two residues splits the cytosolic entrance into two distinct pathways:

:*The bottom border (cytosolic side) features a narrow "thin bottom gate" formed by residues M207 and F442. The interaction between these two residues splits the cytosolic entrance into two distinct pathways:

:::*Path A: Located between TM2 and TM11.

::*Path A: Located between TM2 and TM11.

:::*Path B: Located between TM5 and TM8.

::*Path B: Located between TM5 and TM8.

::*This suggests that aromatic residues located at the top border are important for extracellular anion binding, while residues at the bottom play a role in exporting extracellular anions to the cytoplasmic side.

:*This suggests that aromatic residues located at the top border are important for extracellular anion binding, while residues at the bottom play a role in exporting extracellular anions to the cytoplasmic side.

*'''Conformational State:'''

::*In the apo state, the transporter is in a relaxed, inward-open conformation, providing access for substrates from the cytoplasm.

:*In the apo state, the transporter is in a relaxed, inward-open conformation, providing access for substrates from the cytoplasm.

===Olmesartan recognition by hOAT1===

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@@ Line 81: / Line 81: @@
 '''Key Structural Characteristics:'''
 *'''Overall Fold:'''
-::*Adopts the classic Major Facilitator Superfamily (MFS) fold.
+:*Adopts the classic Major Facilitator Superfamily (MFS) fold.
-::*Comprises 12 transmembrane helices (TMs 1-12).
+:*Comprises 12 transmembrane helices (TMs 1-12).
-::*Exhibits pseudo-two-fold symmetry, divided into an N-lobe (TMs 1-6) and a C-lobe (TMs 7-12).
+:*Exhibits pseudo-two-fold symmetry, divided into an N-lobe (TMs 1-6) and a C-lobe (TMs 7-12).
 *'''Central Binding Cavity:'''
-::*The cavity is located between the N-lobe (formed by TM1, TM2, TM4, TM5) and the C-lobe (formed by TM7, TM8, TM10, TM11).
+:*The cavity is located between the N-lobe (formed by TM1, TM2, TM4, TM5) and the C-lobe (formed by TM7, TM8, TM10, TM11).
-::*It possesses a positively charged electrostatic environment, which explains its strong preference for transporting anionic substrates.
+:*It possesses a positively charged electrostatic environment, which explains its strong preference for transporting anionic substrates.
-::*The cavity is lined by 29 residues, forming a hydrophobic and aromatic-rich environment.
+:*The cavity is lined by 29 residues, forming a hydrophobic and aromatic-rich environment.
 *'''Cavity Borders and Cytosolic Gate:'''
-::*The top border (extracellular side) of the cavity is formed by residues including N35, Y230, Y353, and Y354 and are involved in substrate recognition
+:*The top border (extracellular side) of the cavity is formed by residues including N35, Y230, Y353, and Y354 and are involved in substrate recognition
-::*The bottom border (cytosolic side) features a narrow "thin bottom gate" formed by residues M207 and F442. The interaction between these two residues splits the cytosolic entrance into two distinct pathways:
+:*The bottom border (cytosolic side) features a narrow "thin bottom gate" formed by residues M207 and F442. The interaction between these two residues splits the cytosolic entrance into two distinct pathways:
-:::*Path A: Located between TM2 and TM11.
+::*Path A: Located between TM2 and TM11.
-:::*Path B: Located between TM5 and TM8.
+::*Path B: Located between TM5 and TM8.
-::*This suggests that aromatic residues located at the top border are important for extracellular anion binding, while residues at the bottom play a role in exporting extracellular anions to the cytoplasmic side.
+:*This suggests that aromatic residues located at the top border are important for extracellular anion binding, while residues at the bottom play a role in exporting extracellular anions to the cytoplasmic side.
 *'''Conformational State:'''
-::*In the apo state, the transporter is in a relaxed, inward-open conformation, providing access for substrates from the cytoplasm.
+:*In the apo state, the transporter is in a relaxed, inward-open conformation, providing access for substrates from the cytoplasm.
 ===Olmesartan recognition by hOAT1===