Table 3.
Observed residues interacting via hydrogen bonding for each pathway cluster in DAT. We denote the transmembrane (TM) helix the residue belongs to i.e.,1F76 specifies the F76 residue, belonging to TM1. Clusters are identified as intracellular (I) or extracellular (E), followed by a number denoting a specific pathway. Observation of sodium movement which was NA1 in all cases with the substrate is also indicated, as well as how many paths belong to the cluster.
| Setup | Path | # Times | Residues |
|---|---|---|---|
| R6 | E1 | 14 | 1F76, 1R85, I148, 3S149, 3Y156, 6L321, 6G322, 6F325, el4A382, 10D475 |
| I1 | 15 | 1F76, il1G127, il1A128, 3S149, 3Y156, 6L321, 6G322, 6F325, 8G425, 10E490 | |
| I2 | 7 | 1S72, 1F76, 3S149, 3Y156, 6L321,6G322, 6F325, 8S428 | |
| R7 | E1 | 44 | 1W84, 3Y156, el4A382, el4T383, el4D384, el4G385, 10F471, 10T472, 10D475 |
| R8 | E1 | 34† | 1W84, 1R85, el4D384, el4G385, el4P386, 10D475 |
| R9 | E1 | 16 | 1F76, 3I148, 3S149, 3Y156, 6L321, 6F325, el4T383, 8D420, 8G425, 10T472, 10D475 |
| I1 | 3 | 1F76, 3S149, 3Y156, 6L321 | |
| I2 | 3 | 1F76, 3S149, 3Y156, 6L321, 7N339, 7D344, 7T348, 8G425, | |
| I3 | 3 | 1F76, 3S149, 6F325, 8G425 | |
| I4 | 4 | 1F76, 3S149, 3Y156, 6F325, 8E436 | |
| R10 | E1 | 9 | 1F76, 1R85, 3I148, 3S149, 3Y151, 3Y156, el4T383, 8S421, 9A442, 10D475, 10A478 |
| E2 | 12 | 1F76, 1R85, 3I148, 3S149, 3Y156, 6L321, 6F325, el4A382, 10D475 | |
| I1 | 8 | 1D68, 1S72, 1F76, 3S149, 3Y156, 5L254, 6L321, 7N352, 8D420, 8G424, 8G425, 8S428 | |
| R11 | E1 | 17 | 1F76, 1R85, 3I148, 3S149, 3Y156, 6L321, 6F325 |
| I1 | 4 | 1F76, 3S149, 6L321 | |
| I2 | 7 | 1F76, il1A128, il1W132, 3S149, 3Y156, 6L321, 6F325, 8G425, 8S428, 8E436 |
In 16/50 DAT:COC RAMD runs, no hydrogen bonding between the protein and cocaine was observed. Note that this list omits binding pocket residues (as described in Indarte et al.:15 A77, D79, V152, F319, S320, V327, S421and A422) for clarity. A complete list can be found in supporting information.