Table 3 Catalytic residues from the favourable docked complexes and crystal structures of HDACs involved in hydrogen bonding, π-stacking, Zn2+-metal interactions and hydrophobic interactions with sacubitrilat and reference HDAC inhibitors.
Docked complexes of Sacubitrilat/BIR/B65/BDS with 4R7L | Vorinostat (4R7L/4LXZ/4QA0/4BZ6/5EEI) | Trichostatin (5EEF) | Panobinostat (5EF8) | Quisinostat (6HSK) | Recolinostat (5WGL) |
|---|---|---|---|---|---|
Residues involved in Hydrogen bonds | |||||
Gly268/269 | Gly361 | ||||
Tyr378/383 | Tyr308 | Tyr363 | Tyr745 | Tyr306 | Tyr745 |
Met564 | |||||
Lys565 | Lys330 | ||||
Asp98/104 | |||||
His292/573 | His193 | His573/574 | |||
Ser531 | |||||
Residues involved in π-stacking | |||||
Phe314 | Phe314 | Phe202 | Phe583/643 | Phe152/180 | |
Tyr267 | |||||
Involved in Zn2+-metal interactions | |||||
Yes | Yes | Yes | Yes | Yes | Yes |
Residues involved in hydrophobic interactions | |||||
Gln136,Ala137 Tyr267,Val292 His295,Trp311 Phe314,Pro374 Tyr378,Lys565 | Trp311,Leu369 Pro374,Tyr378 | His82, Pro83 Ser150,Gly201 Phe202,His232 Gu360,Trp261 Gly361,Asp32 3Gly362 | Asp460,His46 His573,His574 Gly582,His614 Asp705,Leu712 Gly743 | Asp101,His142 His143,Gly151 Gly206,Phe207 Pro209,Gly210 Leu274,Gly304 | His462,Pro464 Ser531,Gly582 Phe643,Phe583His614,Asp705Pro711,Leu712Gly743 |
