Target Binding Site Detail
| 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 | |||||
| Ligand General Information | Top | ||||
|---|---|---|---|---|---|
| Ligand Name | [3H]cAMP | Ligand Info | |||
| Canonical SMILES | C1C2C(C(C(O2)N3C=NC4=C(N=CN=C43)N)O)OP(=O)(O1)O | ||||
| InChI | 1S/C10H12N5O6P/c11-8-5-9(13-2-12-8)15(3-14-5)10-6(16)7-4(20-10)1-19-22(17,18)21-7/h2-4,6-7,10,16H,1H2,(H,17,18)(H2,11,12,13)/t4-,6-,7-,10-/m1/s1 | ||||
| InChIKey | IVOMOUWHDPKRLL-KQYNXXCUSA-N | ||||
| PubChem Compound ID | 6076 | ||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| PDB ID: 6GYO Structure of human HCN4 hyperpolarization-activated cyclic nucleotide-gated ion channel in complex with cAMP | ||||||
| Method | Electron microscopy | Resolution | 3.40 Å | Mutation | No | [1] |
| 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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| PDB ID: 3OTF Structural basis for the cAMP-dependent gating in human HCN4 channel | ||||||
| Method | X-ray diffraction | Resolution | 2.40 Å | Mutation | No | [2] |
| 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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| PDB ID: 3U11 Tetramerization dynamics of the C-terminus underlies isoform-specific cAMP-gating in HCN channels | ||||||
| Method | X-ray diffraction | Resolution | 2.50 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 DRIGKKN
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| PDB ID: 4HBN Crystal structure of the human HCN4 channel C-terminus carrying the S672R mutation | ||||||
| Method | X-ray diffraction | Resolution | 2.60 Å | Mutation | Yes | [4] |
| PDB Sequence |
SDSSRRQYQE
529 KYKQVEQYMS539 FHKLPPDTRQ549 RIHDYYEHRY559 QGKMFDEESI569 LGELSEPLRE 579 EIINFNCRKL589 VASMPLFANA599 DPNFVTSMLT609 KLRFEVFQPG619 DYIIREGTIG 629 KKMYFIQHGV639 VSVLTGNKET650 KLADGSYFGE660 ICLLTRGRRT670 ARVRADTYCR 680 LYSLSVDNFN690 EVLEEYPMMR700 RAFETVALDR710 LDRIGKKNS
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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 .CMP or .CMP2 or .CMP3 or :3CMP;style chemicals stick;color identity;select .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:672 or .A:673 or .A:710 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
3.973
VAL642
3.482
THR644
4.949
THR650
3.634
LEU652
3.760
TYR657
4.768
PHE658
3.191
GLY659
2.662
GLU660
2.773
ILE661
3.281
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Structure of human HCN4 hyperpolarization-activated cyclic nucleotide-gated ion channel | ||||
| REF 2 | Structural basis for the cAMP-dependent gating in the human HCN4 channel. J Biol Chem. 2010 Nov 19;285(47):37082-91. | ||||
| REF 3 | 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 4 | Local and global interpretations of a disease-causing mutation near the ligand entry path in hyperpolarization-activated cAMP-gated channel. Structure. 2012 Dec 5;20(12):2116-23. | ||||
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