Binding Site Information of Target
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T30286 | Target Info | |||
| Target Name | Hyperpolarization cyclic nucleotide-gated channel 4 (HCN4) | ||||
| Synonyms | Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4 | ||||
| Target Type | Literature-reported Target | ||||
| Gene Name | HCN4 | ||||
| Biochemical Class | Voltage-gated ion channel | ||||
| UniProt ID | |||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| Ligand Name: [3H]cAMP | Ligand Info | |||||
| Structure Description | Structural basis for the cAMP-dependent gating in human HCN4 channel | PDB:3OTF | ||||
| Method | X-ray diffraction | Resolution | 2.40 Å | Mutation | No | [1] |
| PDB Sequence |
DSSRRQYQEK
530 YKQVEQYMSF540 HKLPPDTRQR550 IHDYYEHRYQ560 GKMFDEESIL570 GELSEPLREE 580 IINFNCRKLV590 ASMPLFANAD600 PNFVTSMLTK610 LRFEVFQPGD620 YIIREGTIGK 630 KMYFIQHGVV640 SVLTKGNKET650 KLADGSYFGE660 ICLLTRGRRT670 ASVRADTYCR 680 LYSLSVDNFN690 EVLEEYPMMR700 RAFETVALDR710 LDRIGKK
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: Cysteine Sulfenic Acid | Ligand Info | |||||
| Structure Description | Tetramerization dynamics of the C-terminus underlies isoform-specific cAMP-gating in HCN channels | PDB:3U11 | ||||
| Method | X-ray diffraction | Resolution | 2.50 Å | Mutation | No | [2] |
| PDB Sequence |
DSSRRQYQEK
530 YKQVEQYMSF540 HKLPPDTRQR550 IHDYYEHRYQ560 GKMFDEESIL570 GELSEPLREE 580 IINFNRKLVA591 SMPLFANADP601 NFVTSMLTKL611 RFEVFQPGDY621 IIREGTIGKK 631 MYFIQHGVVS641 VLTKGNKETK651 LADGSYFGEI661 CLLTRGRRTA671 SVRADTYCRL 681 YSLSVDNFNE691 VLEEYPMMRR701 AFETVALDRL711 DRIGKKN
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: Cyclic Guanosine Monophosphate | Ligand Info | |||||
| Structure Description | HCN4 CNBD in complex with cGMP | PDB:4KL1 | ||||
| Method | X-ray diffraction | Resolution | 2.70 Å | Mutation | No | [3] |
| PDB Sequence |
DSSRRQYQEK
530 YKQVEQYMSF540 HKLPPDTRQR550 IHDYYEHRYQ560 GKMFDEESIL570 GELSEPLREE 580 IINFNRKLVA591 SMPLFANADP601 NFVTSMLTKL611 RFEVFQPGDY621 IIREGTIGKK 631 MYFIQHGVVS641 VLTKGNKETK651 LADGSYFGEI661 CLLTRGRRTA671 SVRADTYCRL 681 YSLSVDNFNE691 VLEEYPMMRR701 AFETVALDRL711 DR
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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 .PCG or .PCG2 or .PCG3 or :3PCG;style chemicals stick;color identity;select .A:558 or .A:559 or .A:560 or .A:562 or .A:563 or .A:564 or .A:566 or .A:567 or .A:585 or .A:613 or .A:623 or .A:642 or .A:644 or .A:650 or .A:652 or .A:657 or .A:658 or .A:659 or .A:660 or .A:661 or .A:662 or .A:668 or .A:669 or .A:670 or .A:671 or .A:673 or .A:680 or .A:682 or .A:710 or .A:711 or .A:713; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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ARG558
4.276
TYR559
2.965
GLN560
4.978
LYS562
2.596
MET563
3.270
PHE564
2.881
GLU566
2.790
GLU567
3.823
ASN585
4.912
PHE613
3.578
ILE623
4.028
VAL642
3.716
THR644
4.751
THR650
4.242
LEU652
4.228
TYR657
4.527
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| Ligand Name: 1,2-Diacyl-sn-glycero-3-phosphoinositol | Ligand Info | |||||
| Structure Description | Structure of human HCN4 hyperpolarization-activated cyclic nucleotide-gated ion channel in complex with cAMP | PDB:6GYO | ||||
| Method | Electron microscopy | Resolution | 3.40 Å | Mutation | No | [4] |
| PDB Sequence |
MQRQFGAMLQ
223 PGVNKFSLRM233 FGSQKAVERE243 QERVKSAGFW253 IIHPYSDFRF263 YWDLTMLLLM 273 VGNLIIIPVG283 ITFFKDENTT293 PWIVFNVVSD303 TFFLIDLVLN313 FRTGIVVEDN 323 TEIILDPQRI333 KMKYLKSWFM343 VDFISSIPVD353 YIFLIVETRI363 DSEVYKTARA 373 LRIVRFTKIL383 SLLRLLRLSR393 LIRYIHQWEE403 IFHMTYDLAS413 AVVRIVNLIG 423 MMLLLCHWDG433 CLQFLVPMLQ443 DFPDDCWVSI453 NNMVNNSWGK463 QYSYALFKAM 473 SHMLCIGYGR483 QAPVGMSDVW493 LTMLSMIVGA503 TCYAMFIGHA513 TALIQSLDSS 523 RRQYQEKYKQ533 VEQYMSFHKL543 PPDTRQRIHD553 YYEHRYQGKM563 FDEESILGEL 573 SEPLREEIIN583 FNCRKLVASM593 PLFANADPNF603 VTSMLTKLRF613 EVFQPGDYII 623 REGTIGKKMY633 FIQHGVVSVL643 TKGNKETKLA653 DGSYFGEICL663 LTRGRRTASV 673 RADTYCRLYS683 LSVDNFNEVL693 EEYPMMRRAF703 ETVALDRLDR713 I |
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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 .PIE or .PIE2 or .PIE3 or :3PIE;style chemicals stick;color identity;select .A:227 or .A:229 or .A:258 or .A:259 or .A:260 or .A:263 or .A:264 or .A:267 or .A:401 or .A:404 or .A:405 or .A:406 or .A:407; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: 1,2-Distearoyl-sn-glycero-3-phosphoethanolamine | Ligand Info | |||||
| Structure Description | Structure of human HCN4 hyperpolarization-activated cyclic nucleotide-gated ion channel | PDB:6GYN | ||||
| Method | Electron microscopy | Resolution | 3.40 Å | Mutation | No | [5] |
| PDB Sequence |
MQRQFGAMLQ
223 PGVNKFSLRM233 FGSQKAVERE243 QERVKSAGFW253 IIHPYSDFRF263 YWDLTMLLLM 273 VGNLIIIPVG283 ITFFKDENTT293 PWIVFNVVSD303 TFFLIDLVLN313 FRTGIVVEDN 323 TEIILDPQRI333 KMKYLKSWFM343 VDFISSIPVD353 YIFLIVETRI363 DSEVYKTARA 373 LRIVRFTKIL383 SLLRLLRLSR393 LIRYIHQWEE403 IFHMTYDLAS413 AVVRIVNLIG 423 MMLLLCHWDG433 CLQFLVPMLQ443 DFPDDCWVSI453 NNMVNNSWGK463 QYSYALFKAM 473 SHMLCIGYGR483 QAPVGMSDVW493 LTMLSMIVGA503 TCYAMFIGHA513 TALIQSLDSS 523 RRQYQEKYKQ533 VEQYMSFHKL543 PPDTRQRIHD553 YYEHRYQGKM563 FDEESILGEL 573 SEPLREEIIN583 FNCRKLVASM593 PLFANADPNF603 VTSMLTKLRF613 EVFQPGDYII 623 REGTIGKKMY633 FIQHGVVSVL643 TKGNKETKLA653 DGSYFGEICL663 LTRGRRTASV 673 RADTYCRLYS683 LSVDNFNEVL693 EEYPMMRRAF703 ETVAL
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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 .3PE or .3PE2 or .3PE3 or :33PE;style chemicals stick;color identity;select .A:274 or .A:278 or .A:279 or .A:282 or .A:283 or .A:287 or .A:289 or .A:290 or .A:292 or .A:294 or .A:295 or .A:298 or .A:394 or .A:395 or .A:398 or .A:399 or .A:417 or .A:420 or .A:421 or .A:423 or .A:424 or .A:426 or .A:427 or .A:428 or .A:430 or .A:461 or .A:465 or .A:469 or .A:473 or .A:497 or .A:500 or .A:501 or .A:504 or .A:505 or .A:508; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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VAL274
3.970
ILE278
4.127
ILE279
3.716
VAL282
3.690
GLY283
4.072
PHE287
3.155
ASP289
4.044
GLU290
4.067
THR292
2.686
PRO294
4.488
TRP295
3.543
PHE298
4.320
LEU394
3.856
ILE395
4.168
ILE398
3.761
HIS399
3.076
ARG417
4.020
ASN420
3.374
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: Tubercidin 3',5'-cyclic phosphate | Ligand Info | |||||
| Structure Description | Structure of the cyclic nucleotide-binding domain of HCN4 channel complexed with 7-CH-cAMP | PDB:4NVP | ||||
| Method | X-ray diffraction | Resolution | 2.50 Å | Mutation | No | [6] |
| PDB Sequence |
SPMDSSRRQY
527 QEKYKQVEQY537 MSFHKLPPDT547 RQRIHDYYEH557 RYQGKMFDEE567 SILGELSEPL 577 REEIINFNRK588 LVASMPLFAN598 ADPNFVTSML608 TKLRFEVFQP618 GDYIIREGTI 628 GKKMYFIQHG638 VVSVLTKGNK648 ETKLADGSYF658 GEICLLTRGR668 RTASVRADTY 678 CRLYSLSVDN688 FNEVLEEYPM698 MRRAFETVAL708 DRLDRIGKKN718 |
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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 .7CH or .7CH2 or .7CH3 or :37CH;style chemicals stick;color identity;select .A:623 or .A:642 or .A:650 or .A:652 or .A:657 or .A:658 or .A:659 or .A:660 or .A:661 or .A:662 or .A:663 or .A:668 or .A:669 or .A:670 or .A:671 or .A:673 or .A:710 or .A:711 or .A:713 or .A:714; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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ILE623
3.751
VAL642
3.792
THR650
3.886
LEU652
4.010
TYR657
4.649
PHE658
3.161
GLY659
2.701
GLU660
2.618
ILE661
3.310
CYS662
2.950
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Structural basis for the cAMP-dependent gating in the human HCN4 channel. J Biol Chem. 2010 Nov 19;285(47):37082-91. | ||||
| REF 2 | Tetramerization dynamics of C-terminal domain underlies isoform-specific cAMP gating in hyperpolarization-activated cyclic nucleotide-gated channels. J Biol Chem. 2011 Dec 30;286(52):44811-20. | ||||
| REF 3 | Cyclic dinucleotides bind the C-linker of HCN4 to control channel cAMP responsiveness. Nat Chem Biol. 2014 Jun;10(6):457-62. | ||||
| REF 4 | Structure of human HCN4 hyperpolarization-activated cyclic nucleotide-gated ion channel | ||||
| REF 5 | Structure of human HCN4 hyperpolarization-activated cyclic nucleotide-gated ion channel | ||||
| REF 6 | Cyclic nucleotide mapping of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. ACS Chem Biol. 2014 May 16;9(5):1128-37. | ||||
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