Table 2.
Interactions of quercetin, isoquercitrin, and selected inhibitors with serine/threonine kinases
| Group | Target | PDB ID | Ligand | Hydrogen bonds | Hydrophobic interactions | π–π or cation–π interactions | XP GlideScore (kcal/mol) | MM–GBSA binding energy (kcal/mol) |
|---|---|---|---|---|---|---|---|---|
| AGC | Akt1 | 3MVH | Quercetin | Glu228, Ala230, Asp292 | Leu156, Val164, Ala177, Met227, Tyr229, Met281, Phe438, Phe442 | −9.79 | −64.71 | |
| Isoquercitrin | Glu228, Asp292 | Leu156, Val164, Ala177, Met227, Tyr229, Ala230, Met281, Phe438, Phe442 | −9.86 | −69.79 | ||||
| GSK690693 | Asp439 | Leu156, Phe161, Val164, Ala177, Leu181, Phe236, Phe237, Met281, Tyr437, Phe438 | Phe442 | −5.42 | −64.09 | |||
| Akt2 | 2UW9 | Quercetin | Lys160, Glu230, Ala232, Thr292, Asp293 | Leu158, Val166, Ala179, Met229, Tyr231, Met282, Phe439, Phe443 | −9.97 | −63.45 | ||
| Isoquercitrin | Lys160, Glu236, Lys277, Asp293, Asp440 | Leu158, Val166, Ala179, Met229, Phe238, Phe239, Met282, Phe439, Phe443 | −10.91 | −68.70 | ||||
| GSK690693 | Leu158, Thr213, Asn280, Asp440 | Val166, Ala179, Met229, Tyr231, Ala232, Phe239, Met282, Tyr438, Phe439, Phe443 | −7.10 | −73.94 | ||||
| Aurora | 4J8M | Quercetin | Leu139, Glu211, Ala213, Asp274 | Val147, Ala160, Leu194, Leu210, Tyr212, Leu263, Ala273 | −8.16 | −62.39 | ||
| Isoquercitrin | Glu211, Ala213, Asp274 | Leu139, Val147, Ala160, Leu194, Leu210, Tyr212, Leu263, Ala273, Ala281, Pro282 | −10.22 | −71.01 | ||||
| AT9283 | Ala213, Thr217 | Leu139, Val147, Ala160, Leu194, Leu210, Tyr212, Pro214, Tyr219, Leu263, Ala273, Ala281 | −6.71 | −70.34 | ||||
| RSK2 | 4NW5 | Quercetin | Leu74, Leu150, Asp211 | Val82, Leu147, Ala98, Phe149, Leu200 | −10.14 | −69.17 | ||
| Isoquercitrin | Gln76, Asp148, Leu150, Asn198 | Leu74, Val82, Ala98, Phe149, Leu200, Val131, Leu147 | −12.44 | −88.84 | ||||
| BI-D1870 | Lys72, Leu150 | Leu74, Val82, Ala98, Leu200, Val131, Leu147, Phe149 | −8.41 | −78.42 | ||||
| CaMK | Chk1 | 1ZYS | Quercetin | Lys38, Glu85, Cys87, Asp148 | Leu15, Tyr20, Val23, Ala36, Val68, Leu84, Tyr86, Leu137 | −8.38 | −63.43 | |
| Isoquercitrin | Glu17, Cys87, Asn135, Asp148 | Leu15, Tyr20, Val23, Ala36, Val68, Leu84, Tyr86, Leu137, Phe149 | −11.67 | −79.53 | ||||
| AZD7762 | Glu85, Cys87, Glu91 | Leu15, Tyr20, Val23, Ala36, Leu84, Val68, Tyr86, Leu137 | −7.15 | −83.52 | ||||
| CMGC | CDK2 | 4EK4 | Quercetin | Leu83, Gln131, Asp145 | Ile10, Val18, Ala31, Phe82, Leu134, Ala144 | −9.33 | −64.14 | |
| Isoquercitrin | Thr14, Lys33, Leu83, Gln131, Asp145 | Ile10, Val18, Ala31, Leu134 | −10.49 | −70.09 | ||||
| Dinaciclib | Lys33, Asp86, Lys89 | Ile10, Val18, Ala31, Val64, Phe80, Phe82, Leu83, Leu134, Ala144 | −5.57 | −75.63 | ||||
| ERK2 | 4ZZN | Quercetin | Lys52, Met106, Asp109, Asp165 | Ile29, Ala33, Tyr34, Val37, Ala50, Ile82, Leu105, Leu154, Cys164 | −6.69 | −59.57 | ||
| Isoquercitrin | Gln103, Met106, Asp109, Asp165 | Ile29, Ala33, Tyr34, Val37, Ala50, Ile82, Leu105, Leu154, Lys164 | Lys52 | −8.61 | −68.49 | |||
| SCH772984 | Lys52, Asp104, Lys112 | Ile29, Ala33, Val37, Ala50, Ile82, Leu105, Tyr111, Met106, Leu154, Lys164 | −6.61 | −74.69 | ||||
| p38α | 4R3C | Quercetin | Lys53, Met109, Asp112, Asp168 | Val30, Val38, Ala51, Ile84, Leu108, Ala111, Leu167, Met179, Tyr182 | −6.69 | −44.85 | ||
| Isoquercitrin | His107, Met109, Asp112, Asp168 | Val30, Val38, Ala51, Ile84, Leu108, Leu167, Met179, Tyr182 | −9.31 | −69.86 | ||||
| Doramapimod | Asp168 | Val30, Ala34, Tyr35, Val38, Ala51, Leu75, Ile84, Leu108, Met109, Ala111, Ala157, Leu167, Phe169 | −4.87 | −79.74 | ||||
| JNK1 | 4QTD | Quercetin | Ala36, Lys55, Glu73, Asp151, Asn156, Leu168 | Val40, Ile86, Met108, Leu172, Val187 | −8.20 | −45.53 | ||
| Isoquercitrin | Ala36, Arg69, Asp151, Ser155, Asn156, Leu168 | Val40, Ile86, Met108, Phe170, Leu172, Val186, Val187 | Arg69 | −10.60 | −50.23 | |||
| AS601245 | Lys55, Met111 | Ile32, Ala36, Val40, Ala53, Ile86, Met108, Leu110, Val158, Leu168 | −9.03 | −81.19 | ||||
| GSK3B | 1J1B | Quercetin | Lys85, Val135, Gln185, Asp200 | Ile62, Val70, Ala83, Val110, Leu132, Tyr134, Leu188, Cys199 | −9.29 | −55.35 | ||
| Isoquercitrin | Ile62, Asn64, Lys85, Val135, Arg141, Gln185, Asp200 | Val70, Val110, Leu132, Tyr134, Pro136, Tyr140, Leu188, Cys199, Phe201 | Arg141 | −10.44 | −62.59 | |||
| CHIR-99021 | Ile62, Asn64 | Val70, Ala83, Leu108, Val110, Leu132, Tyr134, Val135, Pro136, Leu188, Cys199 | Lys85, Arg141 | −5.94 | −67.09 | |||
| CLK1 | 1Z57 | Quercetin | Leu167, Lys191, Asp250, Asp325 | Phe172, Val175, Ala189, Val225, Phe241, Leu243, Leu244, Leu295, Val324 | −8.99 | −62.96 | ||
| Isoquercitrin | Gly245, Asp250, Asp325 | Leu167, Phe172, Val175, Ala189, Val225, Phe241, Leu243, Leu244, Leu246, Tyr249 Leu295, Val324 | −10.53 | −73.19 | ||||
| STE | MEK1 | 3VVH | Quercetin | Leu74, Glu144, Met146, Asn195, Asp208 | Ala76, Val82, Ala95, Val127, Met143, Leu197, Cys207 | −9.97 | −64.99 | |
| Isoquercitrin | Met146, Ser194, Asp152, Asp208 | Leu74, Ala76, Val82, Ala95, Met143, Leu197, Cys207 | −9.65 | −68.12 | ||||
| PAK4 | 2Q0N | Quercetin | Glu329, Glu396, Leu398, Asp458 | Ile327, Val335, Ala348, Val379, Met395, Phe397, Leu447 | −10.03 | −58.22 | ||
| Isoquercitrin | Glu396, Leu398, Ala402, Asp458 | Ile327, Val335, Ala348, Val379, Met395, Phe397, Leu447 | −9.86 | −60.47 | ||||
| Plk1 | 2RKU | Quercetin | Leu59, Lys82, Glu131, Cys133, Asp194 | Cys67, Ala80, Val114, Leu130, Leu132, Phe183, Phe195 | −10.89 | −62.84 | ||
| Isoquercitrin | Leu59, Lys82, Glu140, Cys133, Asp194 | Cys67, Ala80, Val114, Leu130, Leu132, Leu139 | Phe183 | −11.26 | −74.86 | |||
| TKL | B-Raf | 5CSW | Quercetin | Cys532, Asp594, Phe595 | Ile463, Phe468, Val471, Ala481, Leu505, Leu514, Ile527, Trp531, Phe583 | −9.48 | −60.46 | |
| Isoquercitrin | Cys532, Gly534, Ser536, Asn580, Phe583, Asp594 | Leu514, Ile463, Val471, Ala481, Trp531, Tyr538 | −11.07 | −67.72 |
Abbreviations: MM–GBSA, molecular mechanics–generalized Born surface area; PDB, Protein Data Bank; XP, extra precision.