Details of the Target

General Information of Target

Target ID LDTP06615
Target Name Kynureninase (KYNU)
Gene Name KYNU
Gene ID 8942
Synonyms
Kynureninase; EC 3.7.1.3; L-kynurenine hydrolase
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MEPSSLELPADTVQRIAAELKCHPTDERVALHLDEEDKLRHFRECFYIPKIQDLPPVDLS
LVNKDENAIYFLGNSLGLQPKMVKTYLEEELDKWAKIAAYGHEVGKRPWITGDESIVGLM
KDIVGANEKEIALMNALTVNLHLLMLSFFKPTPKRYKILLEAKAFPSDHYAIESQLQLHG
LNIEESMRMIKPREGEETLRIEDILEVIEKEGDSIAVILFSGVHFYTGQHFNIPAITKAG
QAKGCYVGFDLAHAVGNVELYLHDWGVDFACWCSYKYLNAGAGGIAGAFIHEKHAHTIKP
ALVGWFGHELSTRFKMDNKLQLIPGVCGFRISNPPILLVCSLHASLEIFKQATMKALRKK
SVLLTGYLEYLIKHNYGKDKAATKKPVVNIITPSHVEERGCQLTITFSVPNKDVFQELEK
RGVVCDKRNPNGIRVAPVPLYNSFHDVYKFTNLLTSILDSAETKN
Target Type
Preclinical
Target Bioclass
Enzyme
Family
Kynureninase family
Subcellular location
Cytoplasm, cytosol
Function
Catalyzes the cleavage of L-kynurenine (L-Kyn) and L-3-hydroxykynurenine (L-3OHKyn) into anthranilic acid (AA) and 3-hydroxyanthranilic acid (3-OHAA), respectively. Has a preference for the L-3-hydroxy form. Also has cysteine-conjugate-beta-lyase activity.
TTD ID
T99912
Uniprot ID
Q16719
DrugMap ID
TTWQM3J
Ensemble ID
ENST00000264170.9
HGNC ID
HGNC:6469
ChEMBL ID
CHEMBL5100

Target Site Mutations in Different Cell Lines

Cell line Mutation details Probe for labeling this protein in this cell
A431 SNV: p.P439T DBIA    Probe Info 
HT115 SNV: p.H343Y .
MCC13 SNV: p.L440F .
NCIH1155 Deletion: p.P108LfsTer10 DBIA    Probe Info 

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 13 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
Probe 1
 Probe Info  		Y86(91.02); Y100(13.25)  LDD3495  [1]
BTD
 Probe Info  		C425(1.19)  LDD1700  [2]
DBIA
 Probe Info  		C45(1.04); C327(1.00)  LDD0078  [3]
5E-2FA
 Probe Info  		H102(0.00); H395(0.00); H32(0.00)  LDD2235  [4]
m-APA
 Probe Info  		H395(0.00); H32(0.00); H102(0.00); H445(0.00)  LDD2231  [4]
IA-alkyne
 Probe Info  		C45(0.00); C22(0.00); C425(0.00); C401(0.00)  LDD0162  [5]
IPM
 Probe Info  		N.A.  LDD0025  [6]
WYneN
 Probe Info  		N.A.  LDD0021  [7]
TFBX
 Probe Info  		C327(0.00); C45(0.00); C22(0.00)  LDD0148  [6]
Acrolein
 Probe Info  		H32(0.00); H445(0.00); H395(0.00); C327(0.00)  LDD0217  [8]
Crotonaldehyde
 Probe Info  		N.A.  LDD0219  [8]
Methacrolein
 Probe Info  		C327(0.00); C45(0.00); C22(0.00)  LDD0218  [8]
NAIA_5
 Probe Info  		C22(0.00); C45(0.00); C327(0.00); C401(0.00)  LDD2223  [9]
PAL-AfBPP Probe
Click To Hide/Show 2 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
DA-2
 Probe Info  		N.A.  LDD0072  [10]
STS-1
 Probe Info  		N.A.  LDD0068  [11]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0524  2-Cyano-N-(2-morpholin-4-yl-ethyl)-acetamide MDA-MB-231 C425(0.95)  LDD2117  [2]
 LDCM0020  ARS-1620 HCC44 C45(1.04); C327(1.00)  LDD0078  [3]
 LDCM0108  Chloroacetamide HeLa H445(0.00); C327(0.00); C425(0.00); C22(0.00)  LDD0222  [8]
 LDCM0632  CL-Sc Hep-G2 C327(0.52)  LDD2227  [9]
 LDCM0107  IAA HeLa H445(0.00); H32(0.00); H395(0.00); H308(0.00)  LDD0221  [8]
 LDCM0022  KB02 769-P C45(1.17); C327(1.12)  LDD2246  [12]
 LDCM0023  KB03 769-P C45(1.51); C327(1.38)  LDD2663  [12]
 LDCM0024  KB05 HMCB C327(1.47)  LDD3312  [12]
 LDCM0109  NEM HeLa H445(0.00); H32(0.00); H395(0.00); H23(0.00)  LDD0223  [8]
 LDCM0506  Nucleophilic fragment 16a MDA-MB-231 C425(0.64)  LDD2099  [2]
 LDCM0516  Nucleophilic fragment 21a MDA-MB-231 C425(0.68); C22(0.53)  LDD2109  [2]
 LDCM0530  Nucleophilic fragment 28a MDA-MB-231 C425(0.81); C22(0.71)  LDD2123  [2]
 LDCM0534  Nucleophilic fragment 30a MDA-MB-231 C425(0.68); C22(0.61)  LDD2127  [2]
 LDCM0536  Nucleophilic fragment 31 MDA-MB-231 C425(1.35)  LDD2129  [2]
 LDCM0542  Nucleophilic fragment 37 MDA-MB-231 C425(0.79)  LDD2135  [2]
 LDCM0543  Nucleophilic fragment 38 MDA-MB-231 C425(1.08); C22(1.12)  LDD2136  [2]
 LDCM0544  Nucleophilic fragment 39 MDA-MB-231 C22(0.81)  LDD2137  [2]
 LDCM0211  Nucleophilic fragment 3b MDA-MB-231 C425(1.19)  LDD1700  [2]
 LDCM0546  Nucleophilic fragment 40 MDA-MB-231 C425(0.75); C22(0.62)  LDD2140  [2]
 LDCM0552  Nucleophilic fragment 6a MDA-MB-231 C425(0.61); C22(0.58)  LDD2146  [2]

The Interaction Atlas With This Target

The Protein(s) Related To This Target

Other
Click To Hide/Show 5 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Myozenin-3 (MYOZ3) Myozenin family Q8TDC0
Cancer/testis antigen 55 (CT55) . Q8WUE5
LIM domain transcription factor LMO4 (LMO4) . P61968
Mitochondrial coiled-coil domain protein 1 (MCCD1) . P59942
Ras association domain-containing protein 3 (RASSF3) . Q86WH2

The Drug(s) Related To This Target

Approved
Click To Hide/Show 1 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Pyridoxal Phosphate Small molecular drug DB00114
Preclinical
Click To Hide/Show 2 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
2-amino-4-[3-hydroxyphenyl]-4-hydroxybutanoic Acid Small molecular drug D17TRG
S-(2-aminophenyl)-l-cysteine S,S-dioxide Small molecular drug D6QA4N
Investigative
Click To Hide/Show 6 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
3,6,9,12,15-pentaoxaheptadecane Small molecular drug D02DWE
3-hydroxydesaminokynurenine Small molecular drug D0V4AX
3-hydroxyhippuric Acid Small molecular drug D05JZS
3-methoxydesaminokynurenine Small molecular drug D00ASH
Alanine Small molecular drug DB00160
M-hydroxyhippuric Acid Small molecular drug DB07069

References

1 An Azo Coupling-Based Chemoproteomic Approach to Systematically Profile the Tyrosine Reactivity in the Human Proteome. Anal Chem. 2021 Jul 27;93(29):10334-10342. doi: 10.1021/acs.analchem.1c01935. Epub 2021 Jul 12.
2 Nucleophilic covalent ligand discovery for the cysteine redoxome. Nat Chem Biol. 2023 Nov;19(11):1309-1319. doi: 10.1038/s41589-023-01330-5. Epub 2023 May 29.
Mass spectrometry data entry: PXD039908 , PXD029761
3 Reimagining high-throughput profiling of reactive cysteines for cell-based screening of large electrophile libraries. Nat Biotechnol. 2021 May;39(5):630-641. doi: 10.1038/s41587-020-00778-3. Epub 2021 Jan 4.
4 Global profiling of functional histidines in live cells using small-molecule photosensitizer and chemical probe relay labelling. Nat Chem. 2024 Jun 4. doi: 10.1038/s41557-024-01545-6. Online ahead of print.
Mass spectrometry data entry: PXD042377
5 SP3-FAIMS Chemoproteomics for High-Coverage Profiling of the Human Cysteinome*. Chembiochem. 2021 May 14;22(10):1841-1851. doi: 10.1002/cbic.202000870. Epub 2021 Feb 18.
Mass spectrometry data entry: PXD023056 , PXD023059 , PXD023058 , PXD023057 , PXD023060
6 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
7 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
8 ACR-Based Probe for the Quantitative Profiling of Histidine Reactivity in the Human Proteome. J Am Chem Soc. 2023 Mar 8;145(9):5252-5260. doi: 10.1021/jacs.2c12653. Epub 2023 Feb 27.
9 N-Acryloylindole-alkyne (NAIA) enables imaging and profiling new ligandable cysteines and oxidized thiols by chemoproteomics. Nat Commun. 2023 Jun 15;14(1):3564. doi: 10.1038/s41467-023-39268-w.
Mass spectrometry data entry: PXD041264
10 Cell-based proteome profiling of potential dasatinib targets by use of affinity-based probes. J Am Chem Soc. 2012 Feb 15;134(6):3001-14. doi: 10.1021/ja208518u. Epub 2012 Feb 1.
11 Proteome profiling reveals potential cellular targets of staurosporine using a clickable cell-permeable probe. Chem Commun (Camb). 2011 Oct 28;47(40):11306-8. doi: 10.1039/c1cc14824a. Epub 2011 Sep 16.
12 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