Target Binding Site Detail
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T25956 | Target Info | |||
| Target Name | Histone acetyltransferase p300 (EP300) | ||||
| Synonyms | p300 HAT; Protein propionyltransferase p300; P300; Histone crotonyltransferase p300; Histone butyryltransferase p300; E1Aassociated protein p300; E1A-associated protein p300 | ||||
| Target Type | Clinical trial Target | ||||
| Gene Name | EP300 | ||||
| Biochemical Class | Acyltransferase | ||||
| UniProt ID | |||||
| Ligand General Information | Top | ||||
|---|---|---|---|---|---|
| Ligand Name | Coenzyme A | Ligand Info | |||
| Canonical SMILES | CC(C)(COP(=O)(O)OP(=O)(O)OCC1C(C(C(O1)N2C=NC3=C(N=CN=C32)N)O)OP(=O)(O)O)C(C(=O)NCCC(=O)NCCS)O | ||||
| InChI | 1S/C21H36N7O16P3S/c1-21(2,16(31)19(32)24-4-3-12(29)23-5-6-48)8-41-47(38,39)44-46(36,37)40-7-11-15(43-45(33,34)35)14(30)20(42-11)28-10-27-13-17(22)25-9-26-18(13)28/h9-11,14-16,20,30-31,48H,3-8H2,1-2H3,(H,23,29)(H,24,32)(H,36,37)(H,38,39)(H2,22,25,26)(H2,33,34,35)/t11-,14-,15-,16+,20-/m1/s1 | ||||
| InChIKey | RGJOEKWQDUBAIZ-IBOSZNHHSA-N | ||||
| PubChem Compound ID | 87642 | ||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| PDB ID: 5LKU Crystal structure of the p300 acetyltransferase catalytic core with coenzyme A. | ||||||
| Method | X-ray diffraction | Resolution | 3.50 Å | Mutation | Yes | [1] |
| PDB Sequence |
IFKPEELRQA
1057 LMPTLEALYR1067 QDPESLPFRQ1077 PVDPQLLGIP1087 DYFDIVKSPM1097 DLSTIKRKLD 1107 TGQYQEPWQY1117 VDDIWLMFNN1127 AWLYNRKTSR1137 VYKYCSKLSE1147 VFEQEIDPVM 1157 QSLGYCCGRK1167 LEFSPQTLCC1177 YGKQLCTIPR1187 DATYYSYQNR1197 YHFCEKCFNE 1207 IQGESVSLGQ1223 TTINKEQFSK1233 RKNDTLDPEL1243 FVECTECGRK1253 MHQICVLHHE 1263 IIWPAGFVCD1273 GCLKKSARTR1283 KENKFSAKRL1293 PSTRLGTFLE1303 NRVNDFLRRQ 1313 NHPESGEVTV1323 RVVHASDKTV1333 EVKPGMKARF1343 VDSGEMAESF1353 PYRTKALFAF 1363 EEIDGVDLCF1373 FGMHVQEYGS1383 DCPPPNQRRV1393 YISYLDSVHF1403 FRPKCLRTAV 1413 YHEILIGYLE1423 YVKKLGYTTG1433 HIWACPPSEG1443 DDYIFHCHPP1453 DQKIPKPKRL 1463 QEWFKKMLDK1473 AVSERIVHDY1483 KDIFKQATED1493 RLTSAKELPY1503 FEGDFWPNVL 1513 EESIKESGGS1523 SQKLYATMEK1590 HKEVFFVIRL1600 IAGPAANSLP1610 PIVDPDPLIP 1620 CDLMDGRDAF1630 LTLARDKHLE1640 FSSLRRAQWS1650 TMCMLVELHT1660 Q |
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|
|
PHE1374
4.931
LEU1398
3.473
ASP1399
3.597
SER1400
2.711
ARG1410
2.655
THR1411
2.548
TYR1414
3.344
TRP1436
3.570
ALA1437
4.318
CYS1438
3.538
PRO1439
3.972
|
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| PDB ID: 4PZR Crystal structure of p300 histone acetyltransferase domain in complex with Coenzyme A | ||||||
| Method | X-ray diffraction | Resolution | 2.10 Å | Mutation | Yes | [2] |
| PDB Sequence |
KFSAKRLPST
1296 RLGTFLENRV1306 NDFLRRQNHP1316 ESGEVTVRVV1326 HASDKTVEVK1336 PGMKARFVDS 1346 GEMAESFPYR1356 TKALFAFEEI1366 DGVDLCFFGM1376 HVQEYGSDCP1386 PPNQRRVYIS 1396 YLDSVHFFRP1406 KCLRTAVYHE1416 ILIGYLEYVK1426 KLGYTTGHIW1436 ACPPSEGDDY 1446 IFHCHPPDQK1456 IPKPKRLQEW1466 FKKMLDKAVS1476 ERIVHDYKDI1486 FKQATEDRLT 1496 SAKELPYFEG1506 DFWPNVLEES1516 IKELEQEEEE1526 RKREENDLSQ1582 KLYATMEKHK 1592 EVFFVIRLIA1602 GPAANSLPPI1612 VDPDPLIPCD1622 LMDGRDAFLT1632 LARDKHLEFS 1642 SLRRAQWSTM1652 CMLVELHTQS1662 QD
|
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|
|
SER1396
4.859
TYR1397
3.956
LEU1398
3.107
ASP1399
3.636
SER1400
2.611
LYS1407
4.907
ARG1410
2.829
THR1411
2.777
TYR1414
3.142
TRP1436
4.200
ALA1437
4.812
CYS1438
3.195
PRO1439
3.708
|
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| PDB ID: 6PF1 Crystal structure of the p300 acetyltransferase domain with allosteric inhibitor CPI-090 and CoA | ||||||
| Method | X-ray diffraction | Resolution | 2.32 Å | Mutation | Yes | [3] |
| PDB Sequence |
NLYFQGSKFS
1289 AKRLPSTRLG1299 TFLENRVNDF1309 LRRQNHPESG1319 EVTVRVVHAS1329 DKTVEVKPGM 1339 KARFVDSGEM1349 AESFPYRTKA1359 LFAFEEIDGV1369 DLCFFGMHVQ1379 EYGSDCPPPN 1389 QRRVYISYLD1399 SVHFFRPKCL1409 RTAVYHEILI1419 GYLEYVKKLG1429 YTTGHIWACP 1439 PSEGDDYIFH1449 CHPPDQKIPK1459 PKRLQEWFKK1469 MLDKAVSERI1479 VHDYKDIFKQ 1489 ATEDRLTSAK1499 ELPYFEGDFW1509 PNVLEESIKE1519 SSQKLYATME1589 KHKEVFFVIR 1599 LIAGPAANSL1609 PPIVDPDPLI1619 PCDLMDGRDA1629 FLTLARDKHL1639 EFSSLRRAQW 1649 STMCMLVELH1659 TQ
|
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|
|
SER1396
4.421
TYR1397
4.043
LEU1398
3.194
ASP1399
3.571
SER1400
2.920
ARG1410
2.827
THR1411
2.669
TYR1414
3.365
TRP1436
3.557
ALA1437
4.614
CYS1438
3.551
PRO1439
3.943
|
|||||
| PDB ID: 6PGU Crystal structure of the p300 acetyltransferase domain with allosteric inhibitor CPI-076 and CoA | ||||||
| Method | X-ray diffraction | Resolution | 1.72 Å | Mutation | Yes | [3] |
| PDB Sequence |
SKFSAKRLPS
1295 TRLGTFLENR1305 VNDFLRRQNH1315 PESGEVTVRV1325 VHASDKTVEV1335 KPGMKARFVD 1345 SGEMAESFPY1355 RTKALFAFEE1365 IDGVDLCFFG1375 MHVQEYGSDC1385 PPPNQRRVYI 1395 SYLDSVHFFR1405 PKCLRTAVYH1415 EILIGYLEYV1425 KKLGYTTGHI1435 WACPPSEGDD 1445 YIFHCHPPDQ1455 KIPKPKRLQE1465 WFKKMLDKAV1475 SERIVHDYKD1485 IFKQATEDRL 1495 TSAKELPYFE1505 GDFWPNVLEE1515 SIQKLYATME1589 KHKEVFFVIR1599 LIAGPAANSL 1609 PPIVDPDPLI1619 PCDLMDGRDA1629 FLTLARDKHL1639 EFSSLRRAQW1649 STMCMLVELH 1659 TQS
|
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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 .COA or .COA2 or .COA3 or :3COA;style chemicals stick;color identity;select .A:1396 or .A:1397 or .A:1398 or .A:1399 or .A:1400 or .A:1410 or .A:1411 or .A:1414 or .A:1436 or .A:1437 or .A:1438 or .A:1439 or .A:1440 or .A:1446 or .A:1455 or .A:1456 or .A:1457 or .A:1458 or .A:1459 or .A:1462 or .A:1463 or .A:1466 or .A:1467; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
SER1396
4.696
TYR1397
4.156
LEU1398
3.103
ASP1399
3.606
SER1400
2.528
ARG1410
2.743
THR1411
2.687
TYR1414
3.372
TRP1436
3.520
ALA1437
4.577
CYS1438
3.826
PRO1439
3.653
|
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| PDB ID: 6V8K Crystal structure of the p300 acetyltransferase domain with peptide-competitive inhibitor 2 | ||||||
| Method | X-ray diffraction | Resolution | 1.84 Å | Mutation | Yes | [4] |
| PDB Sequence |
SKFSAKRLPS
1295 TRLGTFLENR1305 VNDFLRRQNH1315 PESGEVTVRV1325 VHASDKTVEV1335 KPGMKARFVD 1345 SGEMAESFPY1355 RTKALFAFEE1365 IDGVDLCFFG1375 MHVQEYGSDC1385 PPPNQRRVYI 1395 SYLDSVHFFR1405 PKCLRTAVYH1415 EILIGYLEYV1425 KKLGYTTGHI1435 WACPPSEGDD 1445 YIFHCHPPDQ1455 KIPKPKRLQE1465 WFKKMLDKAV1475 SERIVHDYKD1485 IFKQATEDRL 1495 TSAKELPYFE1505 GDFWPNVLEE1515 SIKEQKLYAT1587 MEKHKEVFFV1597 IRLIAGPAAN 1607 SLPPIVDPDP1617 LIPCDLMDGR1627 DAFLTLARDK1637 HLEFSSLRRA1647 QWSTMCMLVE 1657 LHTQS
|
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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 .COA or .COA2 or .COA3 or :3COA;style chemicals stick;color identity;select .A:1395 or .A:1396 or .A:1397 or .A:1398 or .A:1399 or .A:1400 or .A:1407 or .A:1410 or .A:1411 or .A:1414 or .A:1436 or .A:1437 or .A:1438 or .A:1439 or .A:1440 or .A:1446 or .A:1451 or .A:1455 or .A:1456 or .A:1457 or .A:1458 or .A:1459 or .A:1462 or .A:1463 or .A:1466 or .A:1467; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
ILE1395
4.996
SER1396
4.562
TYR1397
3.972
LEU1398
2.980
ASP1399
3.556
SER1400
2.544
LYS1407
4.639
ARG1410
2.836
THR1411
2.758
TYR1414
3.303
TRP1436
4.205
ALA1437
4.917
CYS1438
3.604
|
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Structure of p300 in complex with acyl-CoA variants. Nat Chem Biol. 2017 Jan;13(1):21-29. | ||||
| REF 2 | Structure of the p300 histone acetyltransferase bound to acetyl-coenzyme A and its analogues. Biochemistry. 2014 Jun 3;53(21):3415-22. | ||||
| REF 3 | Make the right measurement: Discovery of an allosteric inhibition site for p300-HAT. Struct Dyn. 2019 Oct 11;6(5):054702. | ||||
| REF 4 | Early Drug-Discovery Efforts towards the Identification of EP300/CBP Histone Acetyltransferase (HAT) Inhibitors. ChemMedChem. 2020 Jun 4;15(11):955-960. | ||||
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