Table 1.
Characteristics of melatonin target proteins.
| Protein family | Melatonin target | Affinity/Efficacy for melatonin | Effect of melatonin | Direct binding of melatonin | References | Reviews | |||
|---|---|---|---|---|---|---|---|---|---|
| YES/NO | Methodology | Type of binding site | Independent replication (14) | ||||||
| Receptor | MT1 | 0.1 nM (Kd) (1) | Activation | YES | Ligand binding, co-crystal structure | Orthosteric (co-cyrstal, pharmacol.) | YES | (5, 6) | (7, 8) |
| MT2 | 0.1 nM (Kd) (1) | Activation | YES | Ligand binding, co-crystal structure | Orthosteric (co-cyrstal, pharmacol.) | YES | (6, 9) | (7, 8) | |
| Mel1c | 1 nM (Ki) (2) | Activation | YES | Ligand binding | Orthosteric (pharmacol.) | YES | (10, 11) | ||
| CAND2 | 10 nM (Ki) (2) | Activation | YES | Ligand binding | Unknown | NO | (12) | ||
| ROR/RZR | 5 nM (Kd) (3) | activation | YES | Ligand binding | unknown | unsuccessful | (13, 14) | (15) | |
| VDR | 20 μM (Kd) (4) | Increases affinity of Runx2 for VDR | YES | Isothermal titration calorimetry | The C-terminal ligand binding domain (LBD) of the VDR | NO | (16) | ||
| Enzyme | QR2 | 1 μM (Kd) (4) | Inhibition | YES | Ligand binding, isothermal titration calorimetry, co-crystal structure | Catalytic site (co-crystal) | YES | (17, 18) | (19) |
| MMP-9 | 50–100 μM (IC50) (5) | Inhibition | YES (12) | Docking studies, gelatin zymography assay | Catalytic site (docking) | NO | (20) | ||
| Pepsin | 10 μM (Kd) (4)(6) | Unknown | YES | Isothermal titration calorimetry, equilibrium microdialysis | Catalytic site (docking) | NO | (21) | ||
| PP2A | Unknown | Suppression of PP2A inhibitor effect (11) | YES (12) | Docking studies | Near the catalyt sites (docking) | NO | (22) | (23) | |
| Transporter | PEPT1/2 | 0.5–1 mM (Km) (7) | Transport of melatonin into cells and mitochondria | YES (12) | Docking studies | Substrate site (docking), competion with classical substrates | NO | (24) | |
| GLUT1 | Unknown | Transport of melatonin into cytoplasm, mitochondria | YES (12) | Docking studies | Substrate site (docking), competion with classical substrates | NO | (25) | (26) | |
| Hyp-1 | Unknown (low affinity) | Binding of melatonin (11) | YES | Co-crystal strcuture | Binding site (2 sites) (co-crystal) | NO (13) | (27) | ||
| LLPR-10.2B | Unknown (low affinity) | Binding of melatonin (11) | YES | Co-crystal strcuture | Binding site (2 sites) (co-crystal) | NO (13) | (28) | ||
| Others | mtPTP | 0.8 μM (IC50) (8) | Inhibition of open propability | YES (12) | Electrophysiology | Unknown | NO | (29) | |
| Serum albumin | 10 μM (Kd) (4)(9) | Binding | YES | Ligand binding, isothermal titration calorimetry, absorption spectroscopic | Binding site | YES | (30, 31) | ||
| CaM | >2 mM (Kd) (10) | YES | Fluorescence spectroscopy, NMR and molecular dynamics studies (recomb. protein) | Binding site | YES | (32, 33) | |||
| 1 nM−1 μM (IC50) (5) | Inhibition | YES (12) | Docking studies, enzyme activity | Binding site at CaM in complex with effectors | YES | (34–36) | |||
| Calreticuline | 1 nM (Kd) (3) | Unknown | YES | Ligand binding | Unknown | NO | (37) | ||
(1) [3H]-MLT saturation binding; (2) [125I]-MLT competition binding; (3) [125I]I-MLT saturation binding; (4) isothermal titration calorimetry; (5) enzyme activity inhibition; (6) Equilibrium microdialysis; (7) transport into cells; (8) inhibition of opening of mPTP; (9) Absorption spectroscopy; (10) Fluorescence spectroscopy, NMR; (11) hypothetical; (12) suggested; (13) shown for another member of the PR-10 protein family; (14) refers to the replication of the key results (binding of melatonin to targets) by another group in an independent article.