Structure of PDB 4j14 Chain A Binding Site BS02

Receptor Information
>4j14 Chain A (length=436) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
GGRVLQDVFLDWAKKYGPVVRVNVFHKTSVIVTSPESVKKFLMSTKYNKD
SKMYRALQTVFGERLFGQGLVSECNYERWHKQRRVIDLAFSRSSLVSLME
TFNEKAEQLVEILEAKADGQTPVSMQDMLTYTAMDILAKAAFGMETSMLL
GAQKPLSQAVKLMLEGITASRNTLAKFLPGKRKQLREVRESIRFLRQVGR
DWVQRRREALKRGEEVPADILTQILKAEEGAQDDEGLLDNFVTFFIAGHE
TSANHLAFTVMELSRQPEIVARLQAEVDEVIGSKRYLDFEDLGRLQYLSQ
VLKESLRLYPPAWGTFRLLEEETLIDGVRVPGNTPLLFSTYVMGRMDTYF
EDPLTFNPDRFGPGAPKPRFTYFPFSLGHRSCIGQQFAQMEVKVVMAKLL
QRLEFRLVPGQRFGLQEQATLKPLDPVLCTLRPRGW
Ligand information
Ligand IDX2N
InChIInChI=1S/C37H42F2N8O4/c1-3-35(26(2)48)47-36(49)46(25-42-47)31-7-5-29(6-8-31)43-14-16-44(17-15-43)30-9-11-32(12-10-30)50-20-27-19-37(51-21-27,22-45-24-40-23-41-45)33-13-4-28(38)18-34(33)39/h4-13,18,23-27,35,48H,3,14-17,19-22H2,1-2H3/t26-,27+,35-,37-/m0/s1
InChIKeyRAGOYPUPXAKGKH-XAKZXMRKSA-N
SMILES
SoftwareSMILES
CACTVS 3.352CC[C@@H]([C@H](C)O)N1N=CN(C1=O)c2ccc(cc2)N3CCN(CC3)c4ccc(OC[C@@H]5CO[C@@](C5)(Cn6cncn6)c7ccc(F)cc7F)cc4
ACDLabs 10.04O=C1N(N=CN1c2ccc(cc2)N7CCN(c6ccc(OCC3CC(OC3)(c4ccc(F)cc4F)Cn5ncnc5)cc6)CC7)C(CC)C(O)C
OpenEye OEToolkits 1.6.1CCC(C(C)O)N1C(=O)N(C=N1)c2ccc(cc2)N3CCN(CC3)c4ccc(cc4)OCC5CC(OC5)(Cn6cncn6)c7ccc(cc7F)F
OpenEye OEToolkits 1.6.1CC[C@@H]([C@H](C)O)N1C(=O)N(C=N1)c2ccc(cc2)N3CCN(CC3)c4ccc(cc4)OC[C@H]5C[C@](OC5)(Cn6cncn6)c7ccc(cc7F)F
CACTVS 3.352CC[CH]([CH](C)O)N1N=CN(C1=O)c2ccc(cc2)N3CCN(CC3)c4ccc(OC[CH]5CO[C](C5)(Cn6cncn6)c7ccc(F)cc7F)cc4
FormulaC37 H42 F2 N8 O4
NamePOSACONAZOLE
ChEMBLCHEMBL1397
DrugBankDB01263
ZINCZINC000003938482
PDB chain4j14 Chain A Residue 602 [Download ligand structure] [Download structure with residue number starting from 1] [View ligand structure]
Receptor-Ligand Complex Structure
Global viewLocal viewStructure summary

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PDB4j14 Antifungal Azoles: Structural Insights into Undesired Tight Binding to Cholesterol-Metabolizing CYP46A1.
Resolution2.5 Å
Binding residue
(original residue number in PDB)		F80 M108 A111 F121 V126 R226 I301 A302 T306 F371 T475
Binding residue
(residue number reindexed from 1)		F25 M53 A56 F66 V71 R171 I246 A247 T251 F316 T420
Annotation score1
Binding affinityMOAD: Kd=30nM
Enzymatic activity
Catalytic site (original residue number in PDB) T306 F430 C437
Catalytic site (residue number reindexed from 1) T251 F375 C382
Enzyme Commision number 1.14.14.25: cholesterol 24-hydroxylase.
Gene Ontology
Molecular Function
GO:0004497 monooxygenase activity
GO:0005506 iron ion binding
GO:0008395 steroid hydroxylase activity
GO:0016705 oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen
GO:0020037 heme binding
GO:0033781 cholesterol 24-hydroxylase activity
GO:0046872 metal ion binding
GO:0062184 testosterone 16-beta-hydroxylase activity
Biological Process
GO:0006699 bile acid biosynthetic process
GO:0006707 cholesterol catabolic process
GO:0006805 xenobiotic metabolic process
GO:0007399 nervous system development
GO:0008203 cholesterol metabolic process
GO:0008207 C21-steroid hormone metabolic process
GO:0016125 sterol metabolic process
GO:0042448 progesterone metabolic process
GO:1900271 regulation of long-term synaptic potentiation
GO:1903044 protein localization to membrane raft
Cellular Component
GO:0005783 endoplasmic reticulum
GO:0005789 endoplasmic reticulum membrane
GO:0016020 membrane
GO:0030425 dendrite
GO:0042995 cell projection
GO:0045202 synapse
GO:0098793 presynapse
GO:0098794 postsynapse

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Molecular Function
View graph for
Biological Process
View graph for
Cellular Component
External links
PDB RCSB:4j14, PDBe:4j14, PDBj:4j14
PDBsum4j14
PubMed23604141
UniProtQ9Y6A2|CP46A_HUMAN Cholesterol 24-hydroxylase (Gene Name=CYP46A1)

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