Target Information
| Target General Information | Top | |||||
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| Target ID |
T11793
(Former ID: TTDR01444)
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| Target Name |
Cytochrome P450 2B6 (CYP2B6)
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| Synonyms |
Cytochrome P450 IIB1; CYPIIB6; 1,4-cineole 2-exo-monooxygenase
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| Gene Name |
CYP2B6
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| Target Type |
Literature-reported target
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[1] | ||||
| Function |
In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,4-cineole 2-exo-monooxygenase. Cytochromes P450 are a group of heme-thiolate monooxygenases.
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| BioChemical Class |
Paired donor oxygen oxidoreductase
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| UniProt ID | ||||||
| EC Number |
EC 1.14.13.-
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| Sequence |
MELSVLLFLALLTGLLLLLVQRHPNTHDRLPPGPRPLPLLGNLLQMDRRGLLKSFLRFRE
KYGDVFTVHLGPRPVVMLCGVEAIREALVDKAEAFSGRGKIAMVDPFFRGYGVIFANGNR WKVLRRFSVTTMRDFGMGKRSVEERIQEEAQCLIEELRKSKGALMDPTFLFQSITANIIC SIVFGKRFHYQDQEFLKMLNLFYQTFSLISSVFGQLFELFSGFLKYFPGAHRQVYKNLQE INAYIGHSVEKHRETLDPSAPKDLIDTYLLHMEKEKSNAHSEFSHQNLNLNTLSLFFAGT ETTSTTLRYGFLLMLKYPHVAERVYREIEQVIGPHRPPELHDRAKMPYTEAVIYEIQRFS DLLPMGVPHIVTQHTSFRGYIIPKDTEVFLILSTALHDPHYFEKPDAFNPDHFLDANGAL KKTEAFIPFSLGKRICLGEGIARAELFLFFTTILQNFSMASPVAPEDIDLTPQECGVGKI PPTYQIRFLPR Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| ADReCS ID | BADD_A02216 ; BADD_A05962 | |||||
| HIT2.0 ID | T44KU9 | |||||
| Cell-based Target Expression Variations | Top | |||||
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| Cell-based Target Expression Variations | ||||||
| Drug Binding Sites of Target | Top | |||||
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| Ligand Name: Amlodipine | Ligand Info | |||||
| Structure Description | Crystal Structure of P450 2B6 (Y226H/K262R) in complex with two molecules of Amlodipine | PDB:3UA5 | ||||
| Method | X-ray diffraction | Resolution | 2.80 Å | Mutation | Yes | [2] |
| PDB Sequence |
GKLPPGPRPL
37 PLLGNLLQMD47 RRGLLKSFLR57 FREKYGDVFT67 VHLGPRPVVM77 LCGVEAIREA 87 LVDKAEAFSG97 RGKIAMVDPF107 FRGYGVIFAN117 GNRWKVLRRF127 SVTTMRDFGM 137 GKRSVEERIQ147 EEAQCLIEEL157 RKSKGALMDP167 TFLFQSITAN177 IICSIVFGKR 187 FHYQDQEFLK197 MLNLFYQTFS207 LISSVFGQLF217 ELFSGFLKHF227 PGAHRQVYKN 237 LQEINAYIGH247 SVEKHRETLD257 PSAPRDLIDT267 YLLHMEKEKS277 NAHSEFSHQN 287 LNLNTLSLFF297 AGTETTSTTL307 RYGFLLMLKY317 PHVAERVYRE327 IEQVIGPHRP 337 PELHDRAKMP347 YTEAVIYEIQ357 RFSDLLPMGV367 PHIVTQHTSF377 RGYIIPKDTE 387 VFLILSTALH397 DPHYFEKPDA407 FNPDHFLDAN417 GALKKTEAFI427 PFSLGKRICL 437 GEGIARAELF447 LFFTTILQNF457 SMASPVAPED467 IDLTPQECGV477 GKIPPTYQIR 487 FLPRH
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ARG49
3.516
LEU51
3.504
LEU70
4.792
ARG73
3.681
LYS100
4.515
ILE101
3.546
ILE114
3.736
PHE115
3.408
PHE206
3.710
ILE209
4.093
SER210
3.791
GLY214
4.870
GLN215
3.275
GLU218
3.324
LEU219
3.397
PHE297
3.821
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| Ligand Name: (1s,5r)-2-(Bromomethyl)-6,6-Dimethylbicyclo[3.1.1]hept-2-Ene | Ligand Info | |||||
| Structure Description | Crystal Structure of CYP2B6 (Y226H/K262R/I114V) in complex with myrtenyl bromide | PDB:5UFG | ||||
| Method | X-ray diffraction | Resolution | 1.76 Å | Mutation | Yes | [3] |
| PDB Sequence |
KLPPGPRPLP
38 LLGNLLQMDR48 RGLLKSFLRF58 REKYGDVFTV68 HLGPRPVVML78 CGVEAIREAL 88 VDKAEAFSGR98 GKIAMVDPFF108 RGYGVVFANG118 NRWKVLRRFS128 VTTMRDFGMG 138 KRSVEERIQE148 EAQCLIEELR158 KSKGALMDPT168 FLFQSITANI178 ICSIVFGKRF 188 HYQDQEFLKM198 LNLFYQTFSL208 ISSVFGQLFE218 LFSGFLKHFP228 GAHRQVYKNL 238 QEINAYIGHS248 VEKHRETLDP258 SAPRDLIDTY268 LLHMEKEKSN278 AHSEFSHQNL 288 NLNTLSLFFA298 GTETTSTTLR308 YGFLLMLKYP318 HVAERVYREI328 EQVIGPHRPP 338 ELHDRAKMPY348 TEAVIYEIQR358 FSDLLPMGVP368 HIVTQHTSFR378 GYIIPKDTEV 388 FLILSTALHD398 PHYFEKPDAF408 NPDHFLDANG418 ALKKTEAFIP428 FSLGKRICLG 438 EGIARAELFL448 FFTTILQNFS458 MASPVAPEDI468 DLTPQECGVG478 KIPPTYQIRF 488 LPRH
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Tissue Distribution
of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.
The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects
(Nat Rev Drug Discov, 20: 64-81, 2021).
Human Pathway Affiliation
of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.
Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes
(Pharmacol Rev, 58: 259-279, 2006).
Biological Network Descriptors
of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.
The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information
(Front Pharmacol, 9, 1245, 2018;
Curr Opin Struct Biol. 44:134-142, 2017).
Human Similarity Proteins
Human Tissue Distribution
Human Pathway Affiliation
Biological Network Descriptors
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There is no similarity protein (E value < 0.005) for this target
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Note:
If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.
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| KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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| Arachidonic acid metabolism | hsa00590 | Affiliated Target |
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| Class: Metabolism => Lipid metabolism | Pathway Hierarchy | ||
| Retinol metabolism | hsa00830 | Affiliated Target |
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| Class: Metabolism => Metabolism of cofactors and vitamins | Pathway Hierarchy | ||
| Metabolism of xenobiotics by cytochrome P450 | hsa00980 | Affiliated Target |
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| Class: Metabolism => Xenobiotics biodegradation and metabolism | Pathway Hierarchy | ||
| Drug metabolism - cytochrome P450 | hsa00982 | Affiliated Target |
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| Class: Metabolism => Xenobiotics biodegradation and metabolism | Pathway Hierarchy | ||
| Degree | 5 | Degree centrality | 5.37E-04 | Betweenness centrality | 2.64E-04 |
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| Closeness centrality | 1.66E-01 | Radiality | 1.26E+01 | Clustering coefficient | 2.00E-01 |
| Neighborhood connectivity | 8.20E+00 | Topological coefficient | 3.00E-01 | Eccentricity | 11 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Chemical Structure based Activity Landscape of Target | Top |
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| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| Target Regulators | Top | |||||
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| Target-regulating microRNAs | ||||||
| Target-Related Models and Studies | Top | |||||
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| Target QSAR Model | ||||||
| References | Top | |||||
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| REF 1 | DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. | |||||
| REF 2 | Conformational adaptation of human cytochrome P450 2B6 and rabbit cytochrome P450 2B4 revealed upon binding multiple amlodipine molecules. Biochemistry. 2012 Sep 18;51(37):7225-38. | |||||
| REF 3 | Halogen-Pi Interactions in the Cytochrome P450 Active Site: Structural Insights into Human CYP2B6 Substrate Selectivity. ACS Chem Biol. 2017 May 19;12(5):1204-1210. | |||||
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