Target Binding Site Detail
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T92803 | Target Info | |||
| Target Name | Dual-specificity tyrosine-phosphorylation regulated kinase 1A (DYRK1A) | ||||
| Synonyms | hMNB; Protein kinase minibrain homolog; MNBH; MNB; HP86; Dual specificity tyrosine-phosphorylation-regulated kinase 1A; Dual specificity YAK1-related kinase; DYRK | ||||
| Target Type | Patented-recorded Target | ||||
| Gene Name | DYRK1A | ||||
| Biochemical Class | Kinase | ||||
| UniProt ID | |||||
| Ligand General Information | Top | ||||
|---|---|---|---|---|---|
| Ligand Name | L-serine-O-phosphate | Ligand Info | |||
| Canonical SMILES | C(C(C(=O)O)N)OP(=O)(O)O | ||||
| InChI | 1S/C3H8NO6P/c4-2(3(5)6)1-10-11(7,8)9/h2H,1,4H2,(H,5,6)(H2,7,8,9)/t2-/m0/s1 | ||||
| InChIKey | BZQFBWGGLXLEPQ-REOHCLBHSA-N | ||||
| PubChem Compound ID | 68841 | ||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| PDB ID: 4AZE Human DYRK1A in complex with Leucettine L41 | ||||||
| Method | X-ray diffraction | Resolution | 3.15 Å | Mutation | No | [1] |
| PDB Sequence |
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| PDB ID: 4NCT Human DYRK1A in complex with PKC412 | ||||||
| Method | X-ray diffraction | Resolution | 2.60 Å | Mutation | No | [2] |
| PDB Sequence |
KVYNDGYDDD
143 NYDYIVKNGE153 KWMDRYEIDS163 LIGKGSFGQV173 VKAYDRVEQE183 WVAIKIIKNK 193 KAFLNQAQIE203 VRLLELMNKH213 DTEMKYYIVH223 LKRHFMFRNH233 LCLVFEMLSY 243 NLYDLLRNTN253 FRGVSLNLTR263 KFAQQMCTAL273 LFLATPELSI283 IHCDLKPENI 293 LLCNPKRAIK304 IVDFGSSCQL314 GQRIYQIQSR325 FYRSPEVLLG335 MPYDLAIDMW 345 SLGCILVEMH355 TGEPLFSGAN365 EVDQMNKIVE375 VLGIPPAHIL385 DQAPKARKFF 395 EKLPDGTWNL405 KKREYKPPGT420 RKLHNILGVE430 TGGPGGRRAG440 ESGHTVADYL 450 KFKDLILRML460 DYDPKTRIQP470 YYALQHSFF
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| PDB ID: 7AKA Structure of DYRK1A in complex with compound 54 | ||||||
| Method | X-ray diffraction | Resolution | 1.90 Å | Mutation | No | [3] |
| PDB Sequence |
PRGHMIVKNG
152 EKWMDRYEID162 SLIGKGSFGQ172 VVKAYDRVEQ182 EWVAIKIIKN192 KKAFLNQAQI 202 EVRLLELMNK212 HDTEMKYYIV222 HLKRHFMFRN232 HLCLVFEMLS242 YNLYDLLRNT 252 NFRGVSLNLT262 RKFAQQMCTA272 LLFLATPELS282 IIHCDLKPEN292 ILLCNPKRSA 302 IKIVDFGSSC312 QLGQRIYQIQ323 SRFYRSPEVL333 LGMPYDLAID343 MWSLGCILVE 353 MHTGEPLFSG363 ANEVDQMNKI373 VEVLGIPPAH383 ILDQAPKARK393 FFEKLPDGTW 403 NLKKYKPPGT420 RKLHNILGVE430 TGGPGGRRAG440 ESGHTVADYL450 KFKDLILRML 460 DYDPKTRIQP470 YYALQHSFFK480 K
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| PDB ID: 7AJV Structure of DYRK1A in complex with compound 38 | ||||||
| Method | X-ray diffraction | Resolution | 2.10 Å | Mutation | No | [3] |
| PDB Sequence |
RGHMIVKNGE
153 KWMDRYEIDS163 LIGKGSFGQV173 VKAYDRVEQE183 WVAIKIIKNK193 KAFLNQAQIE 203 VRLLELMNKH213 DTEMKYYIVH223 LKRHFMFRNH233 LCLVFEMLSY243 NLYDLLRNTN 253 FRGVSLNLTR263 KFAQQMCTAL273 LFLATPELSI283 IHCDLKPENI293 LLCNPKRSAI 303 KIVDFGSSCQ313 LGQRIYQIQS324 RFYRSPEVLL334 GMPYDLAIDM344 WSLGCILVEM 354 HTGEPLFSGA364 NEVDQMNKIV374 EVLGIPPAHI384 LDQAPKARKF394 FEKLPDGTWN 404 LKKTKEYKPP418 GTRKLHNILG428 VETGGPGGRR438 AGESGHTVAD448 YLKFKDLILR 458 MLDYDPKTRI468 QPYYALQHSF478 FKK
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .SEP or .SEP2 or .SEP3 or :3SEP;style chemicals stick;color identity;select .A:143 or .A:144 or .A:146 or .A:147 or .A:190 or .A:191 or .A:192 or .A:193 or .A:233; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 7AK2 Structure of DYRK1A in complex with compound 53 | ||||||
| Method | X-ray diffraction | Resolution | 2.10 Å | Mutation | No | [3] |
| PDB Sequence |
RGHMIVKNGE
153 KWMDRYEIDS163 LIGKGSFGQV173 VKAYDRVEQE183 WVAIKIIKNK193 KAFLNQAQIE 203 VRLLELMNKH213 DTEMKYYIVH223 LKRHFMFRNH233 LCLVFEMLSY243 NLYDLLRNTN 253 FRGVSLNLTR263 KFAQQMCTAL273 LFLATPELSI283 IHCDLKPENI293 LLCNPKRSAI 303 KIVDFGSSCQ313 LGQRIYQIQS324 RFYRSPEVLL334 GMPYDLAIDM344 WSLGCILVEM 354 HTGEPLFSGA364 NEVDQMNKIV374 EVLGIPPAHI384 LDQAPKARKF394 FEKLPDGTWN 404 LKKTKDEYKP417 PGTRKLHNIL427 GVETGGPGGR437 RAGESGHTVA447 DYLKFKDLIL 457 RMLDYDPKTR467 IQPYYALQHS477 FFKK
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .SEP or .SEP2 or .SEP3 or :3SEP;style chemicals stick;color identity;select .A:143 or .A:144 or .A:146 or .A:147 or .A:190 or .A:191 or .A:192 or .A:193 or .A:233; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 7A53 Structure of DYRK1A in complex with compound 7 | ||||||
| Method | X-ray diffraction | Resolution | 2.20 Å | Mutation | No | [4] |
| PDB Sequence |
PRGHMIVKNG
152 EKWMDRYEID162 SLIGKGSFGQ172 VVKAYDRVEQ182 EWVAIKIIKN192 KKAFLNQAQI 202 EVRLLELMNK212 HDTEMKYYIV222 HLKRHFMFRN232 HLCLVFEMLS242 YNLYDLLRNT 252 NFRGVSLNLT262 RKFAQQMCTA272 LLFLATPELS282 IIHCDLKPEN292 ILLCNPKRSA 302 IKIVDFGSSC312 QLGQRIYQIQ323 SRFYRSPEVL333 LGMPYDLAID343 MWSLGCILVE 353 MHTGEPLFSG363 ANEVDQMNKI373 VEVLGIPPAH383 ILDQAPKARK393 FFEKLPDGTW 403 NLKKTEYKPP418 GTRKLHNILG428 VETGGPGGRR438 AGESGHTVAD448 YLKFKDLILR 458 MLDYDPKTRI468 QPYYALQHSF478 FKK
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .SEP or .SEP2 or .SEP3 or :3SEP;style chemicals stick;color identity;select .A:143 or .A:144 or .A:146 or .A:147 or .A:191 or .A:192 or .A:193 or .A:233; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 7AJY Structure of DYRK1A in complex with compound 51 | ||||||
| Method | X-ray diffraction | Resolution | 2.20 Å | Mutation | No | [3] |
| PDB Sequence |
RGHMIVKNGE
153 KWMDRYEIDS163 LIGKGSFGQV173 VKAYDRVEQE183 WVAIKIIKNK193 KAFLNQAQIE 203 VRLLELMNKH213 DTEMKYYIVH223 LKRHFMFRNH233 LCLVFEMLSY243 NLYDLLRNTN 253 FRGVSLNLTR263 KFAQQMCTAL273 LFLATPELSI283 IHCDLKPENI293 LLCNPKRSAI 303 KIVDFGSSCQ313 LGQRIYQIQS324 RFYRSPEVLL334 GMPYDLAIDM344 WSLGCILVEM 354 HTGEPLFSGA364 NEVDQMNKIV374 EVLGIPPAHI384 LDQAPKARKF394 FEKLPDGTWN 404 LKKTKEYKPP418 GTRKLHNILG428 VETGGPGGRR438 AGESGHTVAD448 YLKFKDLILR 458 MLDYDPKTRI468 QPYYALQHSF478 FKK
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .SEP or .SEP2 or .SEP3 or :3SEP;style chemicals stick;color identity;select .A:143 or .A:144 or .A:146 or .A:147 or .A:191 or .A:192 or .A:193 or .A:233; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 7A5N Structure of DYRK1A in complex with compound 34 | ||||||
| Method | X-ray diffraction | Resolution | 2.30 Å | Mutation | No | [4] |
| PDB Sequence |
RGHMIVKNGE
153 KWMDRYEIDS163 LIGKGSFGQV173 VKAYDRVEQE183 WVAIKIIKNK193 KAFLNQAQIE 203 VRLLELMNKH213 DTEMKYYIVH223 LKRHFMFRNH233 LCLVFEMLSY243 NLYDLLRNTN 253 FRGVSLNLTR263 KFAQQMCTAL273 LFLATPELSI283 IHCDLKPENI293 LLCNPKRSAI 303 KIVDFGSSCQ313 LGQRIYQIQS324 RFYRSPEVLL334 GMPYDLAIDM344 WSLGCILVEM 354 HTGEPLFSGA364 NEVDQMNKIV374 EVLGIPPAHI384 LDQAPKARKF394 FEKLPDGTWN 404 LKKTKDEYKP417 PGTRKLHNIL427 GVETGGPGGR437 RAGESGHTVA447 DYLKFKDLIL 457 RMLDYDPKTR467 IQPYYALQHS477 FFKK
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .SEP or .SEP2 or .SEP3 or :3SEP;style chemicals stick;color identity;select .A:143 or .A:144 or .A:146 or .A:147 or .A:191 or .A:192 or .A:193 or .A:233; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 7AKE Structure of DYRK1A in complex with compound 58 | ||||||
| Method | X-ray diffraction | Resolution | 2.30 Å | Mutation | No | [3] |
| PDB Sequence |
VPRGHMIVKN
151 GEKWMDRYEI161 DSLIGKGSFG171 QVVKAYDRVE181 QEWVAIKIIK191 NKKAFLNQAQ 201 IEVRLLELMN211 KHDMKYYIVH223 LKRHFMFRNH233 LCLVFEMLSY243 NLYDLLRNTN 253 FRGVSLNLTR263 KFAQQMCTAL273 LFLATPELSI283 IHCDLKPENI293 LLCNPKRSAI 303 KIVDFGSSCQ313 LGQRIYQIQS324 RFYRSPEVLL334 GMPYDLAIDM344 WSLGCILVEM 354 HTGEPLFSGA364 NEVDQMNKIV374 EVLGIPPAHI384 LDQAPKARKF394 FEKLPDGTWN 404 LKKTYKPPGT420 RKLHNILGVE430 TGGPGGRRAG440 ESGHTVADYL450 KFKDLILRML 460 DYDPKTRIQP470 YYALQHSFFK480 K
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .SEP or .SEP2 or .SEP3 or :3SEP;style chemicals stick;color identity;select .A:143 or .A:144 or .A:146 or .A:147 or .A:191 or .A:192 or .A:193 or .A:233; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 7AKB Structure of DYRK1A in complex with compound 56 | ||||||
| Method | X-ray diffraction | Resolution | 2.80 Å | Mutation | No | [3] |
| PDB Sequence |
PRGHMIVKNG
152 EKWMDRYEID162 SLIGKGSFGQ172 VVKAYDRVEQ182 EWVAIKIIKN192 KKAFLNQAQI 202 EVRLLELMNK212 HDTEMKYYIV222 HLKRHFMFRN232 HLCLVFEMLS242 YNLYDLLRNT 252 NFRGVSLNLT262 RKFAQQMCTA272 LLFLATPELS282 IIHCDLKPEN292 ILLCNPKRSA 302 IKIVDFGSSC312 QLGQRIYQIQ323 SRFYRSPEVL333 LGMPYDLAID343 MWSLGCILVE 353 MHTGEPLFSG363 ANEVDQMNKI373 VEVLGIPPAH383 ILDQAPKARK393 FFEKLPDGTW 403 NLKKYKPPGT420 RKLHNILGVE430 TGGPGGRRAG440 ESGHTVADYL450 KFKDLILRML 460 DYDPKTRIQP470 YYALQHSFFK480 K
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .SEP or .SEP2 or .SEP3 or :3SEP;style chemicals stick;color identity;select .A:143 or .A:144 or .A:146 or .A:147 or .A:191 or .A:192 or .A:193 or .A:233; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 7A4R Structure of DYRK1A in complex with compound 1 | ||||||
| Method | X-ray diffraction | Resolution | 1.80 Å | Mutation | No | [4] |
| PDB Sequence |
VPRGHMIVKN
151 GEKWMDRYEI161 DSLIGKGSFG171 QVVKAYDRVE181 QEWVAIKIIK191 NKKAFLNQAQ 201 IEVRLLELMN211 KHDTEMKYYI221 VHLKRHFMFR231 NHLCLVFEML241 SYNLYDLLRN 251 TNFRGVSLNL261 TRKFAQQMCT271 ALLFLATPEL281 SIIHCDLKPE291 NILLCNPKRS 301 AIKIVDFGSS311 CQLGQRIYQI322 QSRFYRSPEV332 LLGMPYDLAI342 DMWSLGCILV 352 EMHTGEPLFS362 GANEVDQMNK372 IVEVLGIPPA382 HILDQAPKAR392 KFFEKLPDGT 402 WNLKKTKDEY415 KPPGTRKLHN425 ILGVETGGPG435 GRRAGESGHT445 VADYLKFKDL 455 ILRMLDYDPK465 TRIQPYYALQ475 HSFFA
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .SEP or .SEP2 or .SEP3 or :3SEP;style chemicals stick;color identity;select .A:143 or .A:144 or .A:146 or .A:147 or .A:190 or .A:191 or .A:192 or .A:193 or .A:233; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 7A52 Structure of DYRK1A in complex with compound 6 | ||||||
| Method | X-ray diffraction | Resolution | 2.10 Å | Mutation | No | [4] |
| PDB Sequence |
VPRGHMIVKN
151 GEKWMDRYEI161 DSLIGKGSFG171 QVVKAYDRVE181 QEWVAIKIIK191 NKKAFLNQAQ 201 IEVRLLELMN211 KHDTEMKYYI221 VHLKRHFMFR231 NHLCLVFEML241 SYNLYDLLRN 251 TNFRGVSLNL261 TRKFAQQMCT271 ALLFLATPEL281 SIIHCDLKPE291 NILLCNPKRS 301 AIKIVDFGSS311 CQLGQRIYQI322 QSRFYRSPEV332 LLGMPYDLAI342 DMWSLGCILV 352 EMHTGEPLFS362 GANEVDQMNK372 IVEVLGIPPA382 HILDQAPKAR392 KFFEKLPDGT 402 WNLKKTKDEY415 KPPGTRKLHN425 ILGVETGGPG435 GRRAGESGHT445 VADYLKFKDL 455 ILRMLDYDPK465 TRIQPYYALQ475 HSFFAA
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .SEP or .SEP2 or .SEP3 or :3SEP;style chemicals stick;color identity;select .A:143 or .A:144 or .A:146 or .A:147 or .A:190 or .A:191 or .A:192 or .A:193 or .A:233; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 7AJS Structure of DYRK1A in complex with compound 33 | ||||||
| Method | X-ray diffraction | Resolution | 2.15 Å | Mutation | No | [3] |
| PDB Sequence |
VPRGHMIVKN
151 GEKWMDRYEI161 DSLIGKGSFG171 QVVKAYDRVE181 QEWVAIKIIK191 NKKAFLNQAQ 201 IEVRLLELMN211 KHDTEMKYYI221 VHLKRHFMFR231 NHLCLVFEML241 SYNLYDLLRN 251 TNFRGVSLNL261 TRKFAQQMCT271 ALLFLATPEL281 SIIHCDLKPE291 NILLCNPKRS 301 AIKIVDFGSS311 CQLGQRIYQI322 QSRFYRSPEV332 LLGMPYDLAI342 DMWSLGCILV 352 EMHTGEPLFS362 GANEVDQMNK372 IVEVLGIPPA382 HILDQAPKAR392 KFFEKLPDGT 402 WNLKKTKDEY415 KPPGTRKLHN425 ILGVETGGPG435 GRRAGESGHT445 VADYLKFKDL 455 ILRMLDYDPK465 TRIQPYYALQ475 HSFFA
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .SEP or .SEP2 or .SEP3 or :3SEP;style chemicals stick;color identity;select .A:143 or .A:144 or .A:146 or .A:147 or .A:191 or .A:192 or .A:193 or .A:233; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 7AJM Structure of DYRK1A in complex with compound 32 | ||||||
| Method | X-ray diffraction | Resolution | 2.40 Å | Mutation | No | [3] |
| PDB Sequence |
VPRGHMIVKN
151 GEKWMDRYEI161 DSLIGKGSFG171 QVVKAYDRVE181 QEWVAIKIIK191 NKKAFLNQAQ 201 IEVRLLELMN211 KHDTEMKYYI221 VHLKRHFMFR231 NHLCLVFEML241 SYNLYDLLRN 251 TNFRGVSLNL261 TRKFAQQMCT271 ALLFLATPEL281 SIIHCDLKPE291 NILLCNPKRS 301 AIKIVDFGSS311 CQLGQRIYQI322 QSRFYRSPEV332 LLGMPYDLAI342 DMWSLGCILV 352 EMHTGEPLFS362 GANEVDQMNK372 IVEVLGIPPA382 HILDQAPKAR392 KFFEKLPDGT 402 WNLKKTKDEY415 KPPGTRKLHN425 ILGVETGGPG435 GRRAGESGHT445 VADYLKFKDL 455 ILRMLDYDPK465 TRIQPYYALQ475 HSFFA
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .SEP or .SEP2 or .SEP3 or :3SEP;style chemicals stick;color identity;select .A:143 or .A:144 or .A:146 or .A:147 or .A:190 or .A:191 or .A:192 or .A:193 or .A:233; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Selectivity, cocrystal structures, and neuroprotective properties of leucettines, a family of protein kinase inhibitors derived from the marine sponge alkaloid leucettamine B. J Med Chem. 2012 Nov 8;55(21):9312-30. | ||||
| REF 2 | The structure of a dual-specificity tyrosine phosphorylation-regulated kinase 1A-PKC412 complex reveals disulfide-bridge formation with the anomalous catalytic loop HRD(HCD) cysteine. Acta Crystallogr D Biol Crystallogr. 2015 May;71(Pt 5):1207-15. | ||||
| REF 3 | Structure-Guided Discovery of Potent and Selective DYRK1A Inhibitors. J Med Chem. 2021 May 27;64(10):6745-6764. | ||||
| REF 4 | Fragment-Derived Selective Inhibitors of Dual-Specificity Kinases DYRK1A and DYRK1B. J Med Chem. 2021 Jul 8;64(13):8971-8991. | ||||
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