Crystallization (Comment) | Organism |
---|---|
structures in complex with 2-carbamoyl-phenoxy-acetic acid derivatives. Opening of the protein-binding pocket occurs only once an appropriate substituent is attached to the parent substrate scaffold. Up to five water molecules entering the opened pocket cannot stabilize this state. Sole substitution with a benzyl group stabilizes the opened state, and the energetic barrier for opening is estimated to be about 5 kJ/mol. Additional decoration of the pocket-opening benzyl substituent with a nitro group results in a huge enthalpy-driven potency increase. An isosteric carboxylic acid group reduces the potency 1000fold, and binding occurs without pocket opening | Homo sapiens |
Inhibitors | Comment | Organism | Structure |
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(2-carbamoyl-5-fluorophenoxy)acetic acid | the carboxamide nitrogen can undergo a further H-bond to the additionally recruited water molecule W2 that in turn mediates H-bonded contacts involving the additional water molecule W3 to the amide bonds next to Leu300. Using water molecules W2 and W3 as mediating partners, the compound forms additional polar contacts to the protein | Homo sapiens | |
(3-sulfanyl[1,2,5]triazepino[4,3-b]indol-6(3H)-yl)acetic acid | - |
Homo sapiens | |
3-[2-(carboxymethoxy)-4-fluorobenzamido]benzoic acid | the ligand directs its acid group toward the surrounding solvent and accommodates the hydrophobic cleft adjacent to the sealed specificity pocket | Homo sapiens | |
[(3-[[(3-nitrophenyl)methyl]carbamoyl][1,1'-biphenyl]-4-yl)oxy]acetic acid | - |
Homo sapiens | |
[2-(ethynylcarbamoyl)-5-fluorophenoxy]acetic acid | the ligand exhibits a terminal pi-electron rich substituent at the amide function, which fills the cleft between Leu300 and Trp219 next to the sealed specificity pocket | Homo sapiens | |
[2-[(1,3-benzothiazol-2-yl)carbamoyl]-5-fluorophenoxy]acetic acid | an H-bond is formed between the backbone Leu300NH group and the nitrogen atom of the benzothiazolyl moiety | Homo sapiens | |
[5-fluoro-2-(phenylcarbamoyl)phenoxy]acetic acid | ligand is among the weakest of the known ALR2 binders that open the specificity pocket | Homo sapiens | |
[5-fluoro-2-[(3-nitrophenyl)carbamoyl]phenoxy]acetic acid | the ligand opens the specificity pocket with its terminal benzyl moiety and places the meta attached nitro group deeply in the transient pocket | Homo sapiens | |
[5-fluoro-2-[(4,5,7-trifluoro-1,3-benzothiazol-2-yl)carbamoyl]phenoxy]acetic acid | - |
Homo sapiens |
Organism | UniProt | Comment | Textmining |
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Homo sapiens | P15121 | - |
- |