General Information of Target

Target ID LDTP05348
Target Name Sterol 26-hydroxylase, mitochondrial (CYP27A1)
Gene Name CYP27A1
Gene ID 1593
Synonyms
CYP27; Sterol 26-hydroxylase, mitochondrial; EC 1.14.15.15; 5-beta-cholestane-3-alpha,7-alpha,12-alpha-triol 26-hydroxylase; Cytochrome P-450C27/25; Cytochrome P450 27; Sterol 27-hydroxylase; Vitamin D(3) 25-hydroxylase
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MAALGCARLRWALRGAGRGLCPHGARAKAAIPAALPSDKATGAPGAGPGVRRRQRSLEEI
PRLGQLRFFFQLFVQGYALQLHQLQVLYKAKYGPMWMSYLGPQMHVNLASAPLLEQVMRQ
EGKYPVRNDMELWKEHRDQHDLTYGPFTTEGHHWYQLRQALNQRLLKPAEAALYTDAFNE
VIDDFMTRLDQLRAESASGNQVSDMAQLFYYFALEAICYILFEKRIGCLQRSIPEDTVTF
VRSIGLMFQNSLYATFLPKWTRPVLPFWKRYLDGWNAIFSFGKKLIDEKLEDMEAQLQAA
GPDGIQVSGYLHFLLASGQLSPREAMGSLPELLMAGVDTTSNTLTWALYHLSKDPEIQEA
LHEEVVGVVPAGQVPQHKDFAHMPLLKAVLKETLRLYPVVPTNSRIIEKEIEVDGFLFPK
NTQFVFCHYVVSRDPTAFSEPESFQPHRWLRNSQPATPRIQHPFGSVPFGYGVRACLGRR
IAELEMQLLLARLIQKYKVVLAPETGELKSVARIVLVPNKKVGLQFLQRQC
Target Bioclass
Enzyme
Family
Cytochrome P450 family
Subcellular location
Mitochondrion inner membrane
Function
Cytochrome P450 monooxygenase that catalyzes regio- and stereospecific hydroxylation of cholesterol and its derivatives. Hydroxylates (with R stereochemistry) the terminal methyl group of cholesterol side-chain in a three step reaction to yield at first a C26 alcohol, then a C26 aldehyde and finally a C26 acid. Regulates cholesterol homeostasis by catalyzing the conversion of excess cholesterol to bile acids via both the 'neutral' (classic) and the 'acid' (alternative) pathways. May also regulate cholesterol homeostasis via generation of active oxysterols, which act as ligands for NR1H2 and NR1H3 nuclear receptors, modulating the transcription of genes involved in lipid metabolism. Plays a role in cholestanol metabolism in the cerebellum. Similarly to cholesterol, hydroxylates cholestanol and may facilitate sterol diffusion through the blood-brain barrier to the systemic circulation for further degradation. Also hydroxylates retinal 7-ketocholesterol, a noxious oxysterol with pro-inflammatory and pro-apoptotic effects, and may play a role in its elimination from the retinal pigment epithelium. May play a redundant role in vitamin D biosynthesis. Catalyzes 25-hydroxylation of vitamin D3 that is required for its conversion to a functionally active form.
Uniprot ID
Q02318
Ensemble ID
ENST00000258415.9
HGNC ID
HGNC:2605
ChEMBL ID
CHEMBL5992

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 8 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
Alkylaryl probe 2
 Probe Info 
20.00  LDD0391  [1]
YN-1
 Probe Info 
100.00  LDD0444  [2]
YN-4
 Probe Info 
100.00  LDD0445  [2]
DBIA
 Probe Info 
C427(2.04)  LDD3410  [3]
Jackson_14
 Probe Info 
2.27  LDD0123  [4]
CY-1
 Probe Info 
N.A.  LDD0246  [5]
IPM
 Probe Info 
N.A.  LDD0005  [6]
TFBX
 Probe Info 
N.A.  LDD0148  [7]
PAL-AfBPP Probe
Click To Hide/Show 1 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
PARPYnD
 Probe Info 
1.74  LDD0374  [8]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0147  AZ0108 MDA-MB-468 1.46  LDD0376  [8]
 LDCM0022  KB02 A101D C427(1.61)  LDD2250  [3]
 LDCM0023  KB03 A101D C427(3.48)  LDD2667  [3]
 LDCM0024  KB05 RPMI-7951 C427(2.04)  LDD3410  [3]
 LDCM0099  Phenelzine MDA-MB-231 3.00  LDD0392  [1]
 LDCM0016  Ranjitkar_cp1 MDA-MB-231 2.27  LDD0123  [4]

The Interaction Atlas With This Target

The Drug(s) Related To This Target

Approved
Click To Hide/Show 5 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Pegvisomant BiotechDrug DB00082
Chenodeoxycholic Acid Small molecular drug DB06777
Cholecalciferol Small molecular drug DB00169
Doxercalciferol Small molecular drug DB06410
Ergocalciferol Small molecular drug DB00153

References

1 Hydrazines as versatile chemical biology probes and drug-discovery tools for cofactor-dependent enzymes. bioRxiv, 2020-06.
2 Ynamide Electrophile for the Profiling of Ligandable Carboxyl Residues in Live Cells and the Development of New Covalent Inhibitors. J Med Chem. 2022 Aug 11;65(15):10408-10418. doi: 10.1021/acs.jmedchem.2c00272. Epub 2022 Jul 26.
3 DrugMap: A quantitative pan-cancer analysis of cysteine ligandability. Cell. 2024 May 9;187(10):2536-2556.e30. doi: 10.1016/j.cell.2024.03.027. Epub 2024 Apr 22.
Mass spectrometry data entry: PXD047840
4 Appendage and Scaffold Diverse Fully Functionalized Small-Molecule Probes via a Minimalist Terminal Alkyne-Aliphatic Diazirine Isocyanide. J Org Chem. 2018 Sep 21;83(18):11245-11253. doi: 10.1021/acs.joc.8b01831. Epub 2018 Aug 31.
5 Cyclopropenone, Cyclopropeniminium Ion, and Cyclopropenethione as Novel Electrophilic Warheads for Potential Target Discovery of Triple-Negative Breast Cancer. J Med Chem. 2023 Feb 23;66(4):2851-2864. doi: 10.1021/acs.jmedchem.2c01889. Epub 2023 Feb 10.
6 A modification-centric assessment tool for the performance of chemoproteomic probes. Nat Chem Biol. 2022 Aug;18(8):904-912. doi: 10.1038/s41589-022-01074-8. Epub 2022 Jul 21.
Mass spectrometry data entry: PXD027758 , PXD027755 , PXD027760 , PXD027762 , PXD027756 , PXD027591 , PXD007149 , PXD030064 , PXD032392 , PXD027789 , PXD027767 , PXD027764
7 Chemoproteomic Profiling by Cysteine Fluoroalkylation Reveals Myrocin G as an Inhibitor of the Nonhomologous End Joining DNA Repair Pathway. J Am Chem Soc. 2021 Dec 8;143(48):20332-20342. doi: 10.1021/jacs.1c09724. Epub 2021 Nov 24.
Mass spectrometry data entry: PXD029255
8 Structure-Guided Design and In-Cell Target Profiling of a Cell-Active Target Engagement Probe for PARP Inhibitors. ACS Chem Biol. 2020 Feb 21;15(2):325-333. doi: 10.1021/acschembio.9b00963. Epub 2020 Feb 10.