Details of the Target

General Information of Target

Target ID LDTP05198
Target Name Histone H3.3 (H3-3A; H3-3B)
Gene Name H3-3A; H3-3B
Gene ID 3020
Synonyms
H3.3A; H3F3; H3F3A; H3.3B; H3F3B; Histone H3.3
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
Sequence
MARTKQTARKSTGGKAPRKQLATKAARKSAPSTGGVKKPHRYRPGTVALREIRRYQKSTE
LLIRKLPFQRLVREIAQDFKTDLRFQSAAIGALQEASEAYLVGLFEDTNLCAIHAKRVTI
MPKDIQLARRIRGERA
Target Type
Literature-reported
Target Bioclass
Other
Family
Histone H3 family
Subcellular location
Nucleus
Function
Variant histone H3 which replaces conventional H3 in a wide range of nucleosomes in active genes. Constitutes the predominant form of histone H3 in non-dividing cells and is incorporated into chromatin independently of DNA synthesis. Deposited at sites of nucleosomal displacement throughout transcribed genes, suggesting that it represents an epigenetic imprint of transcriptionally active chromatin. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.
TTD ID
T90766
Uniprot ID
P84243
DrugMap ID
TT16NHT
Ensemble ID
ENST00000254810.8
HGNC ID
HGNC:4764

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 22 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
m-APA
 Probe Info  		12.55  LDD0402  [2]
TH211
 Probe Info  		Y42(20.00)  LDD0257  [3]
STPyne
 Probe Info  		K123(2.32); K37(10.00); K80(10.00)  LDD0277  [4]
AZ-9
 Probe Info  		D78(0.98)  LDD2208  [5]
ONAyne
 Probe Info  		K123(0.00); K80(0.00)  LDD0273  [4]
EA-probe
 Probe Info  		C111(1.08); C111(1.10)  LDD2210  [6]
DBIA
 Probe Info  		C111(1.00)  LDD0533  [7]
ATP probe
 Probe Info  		N.A.  LDD0199  [8]
1d-yne
 Probe Info  		K116(0.00); K123(0.00)  LDD0358  [9]
4-Iodoacetamidophenylacetylene
 Probe Info  		N.A.  LDD0038  [10]
IA-alkyne
 Probe Info  		N.A.  LDD0036  [10]
Lodoacetamide azide
 Probe Info  		N.A.  LDD0037  [10]
Alkyne tyramide
 Probe Info  		K80(0.00); K57(0.00)  LDD0003  [11]
ATP probe
 Probe Info  		N.A.  LDD0035  [12]
NAIA_4
 Probe Info  		N.A.  LDD2226  [13]
IPM
 Probe Info  		N.A.  LDD2156  [14]
NHS
 Probe Info  		K57(0.00); K123(0.00); K80(0.00)  LDD0010  [11]
OSF
 Probe Info  		N.A.  LDD0029  [15]
1c-yne
 Probe Info  		N.A.  LDD0228  [9]
AOyne
 Probe Info  		13.60  LDD0443  [16]
NAIA_5
 Probe Info  		N.A.  LDD2223  [13]
HHS-482
 Probe Info  		Y100(1.63)  LDD2239  [17]
PAL-AfBPP Probe
Click To Hide/Show 3 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
C056
 Probe Info  		16.22  LDD1753  [18]
STS-2
 Probe Info  		N.A.  LDD0138  [19]
Photocelecoxib
 Probe Info  		Y42(0.00); S58(0.00)  LDD0019  [20]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0214  AC1 HEK-293T C111(0.98)  LDD1507  [21]
 LDCM0216  AC100 HCT 116 C111(1.00)  LDD0533  [7]
 LDCM0217  AC101 HCT 116 C111(1.30)  LDD0534  [7]
 LDCM0218  AC102 HCT 116 C111(0.71)  LDD0535  [7]
 LDCM0219  AC103 HCT 116 C111(0.73)  LDD0536  [7]
 LDCM0220  AC104 HCT 116 C111(0.91)  LDD0537  [7]
 LDCM0221  AC105 HCT 116 C111(1.24)  LDD0538  [7]
 LDCM0222  AC106 HCT 116 C111(0.75)  LDD0539  [7]
 LDCM0223  AC107 HCT 116 C111(0.69)  LDD0540  [7]
 LDCM0224  AC108 HCT 116 C111(0.68)  LDD0541  [7]
 LDCM0225  AC109 HCT 116 C111(1.34)  LDD0542  [7]
 LDCM0227  AC110 HCT 116 C111(0.67)  LDD0544  [7]
 LDCM0228  AC111 HCT 116 C111(1.33)  LDD0545  [7]
 LDCM0229  AC112 HCT 116 C111(1.85)  LDD0546  [7]
 LDCM0276  AC17 HCT 116 C111(1.42)  LDD0593  [7]
 LDCM0277  AC18 HCT 116 C111(2.75)  LDD0594  [7]
 LDCM0278  AC19 HCT 116 C111(1.02)  LDD0595  [7]
 LDCM0280  AC20 HCT 116 C111(2.22)  LDD0597  [7]
 LDCM0281  AC21 HCT 116 C111(0.77)  LDD0598  [7]
 LDCM0282  AC22 HCT 116 C111(0.99)  LDD0599  [7]
 LDCM0283  AC23 HCT 116 C111(2.30)  LDD0600  [7]
 LDCM0284  AC24 HCT 116 C111(2.82)  LDD0601  [7]
 LDCM0285  AC25 HEK-293T C111(1.05)  LDD1524  [21]
 LDCM0294  AC33 HEK-293T C111(1.09)  LDD1533  [21]
 LDCM0296  AC35 HCT 116 C111(1.28)  LDD0613  [7]
 LDCM0297  AC36 HCT 116 C111(0.90)  LDD0614  [7]
 LDCM0298  AC37 HCT 116 C111(0.96)  LDD0615  [7]
 LDCM0299  AC38 HCT 116 C111(0.88)  LDD0616  [7]
 LDCM0300  AC39 HCT 116 C111(0.81)  LDD0617  [7]
 LDCM0302  AC40 HCT 116 C111(0.71)  LDD0619  [7]
 LDCM0303  AC41 HCT 116 C111(0.80)  LDD0620  [7]
 LDCM0304  AC42 HCT 116 C111(0.84)  LDD0621  [7]
 LDCM0305  AC43 HCT 116 C111(0.89)  LDD0622  [7]
 LDCM0306  AC44 HCT 116 C111(0.66)  LDD0623  [7]
 LDCM0307  AC45 HCT 116 C111(0.72)  LDD0624  [7]
 LDCM0308  AC46 HCT 116 C111(1.35)  LDD0625  [7]
 LDCM0309  AC47 HCT 116 C111(1.07)  LDD0626  [7]
 LDCM0310  AC48 HCT 116 C111(1.50)  LDD0627  [7]
 LDCM0311  AC49 HCT 116 C111(0.60)  LDD0628  [7]
 LDCM0313  AC50 HCT 116 C111(0.68)  LDD0630  [7]
 LDCM0314  AC51 HCT 116 C111(1.51)  LDD0631  [7]
 LDCM0315  AC52 HCT 116 C111(0.79)  LDD0632  [7]
 LDCM0316  AC53 HCT 116 C111(0.87)  LDD0633  [7]
 LDCM0317  AC54 HCT 116 C111(0.96)  LDD0634  [7]
 LDCM0318  AC55 HCT 116 C111(0.71)  LDD0635  [7]
 LDCM0319  AC56 HCT 116 C111(0.59)  LDD0636  [7]
 LDCM0320  AC57 HCT 116 C111(0.73)  LDD0637  [7]
 LDCM0321  AC58 HCT 116 C111(0.83)  LDD0638  [7]
 LDCM0322  AC59 HCT 116 C111(0.56)  LDD0639  [7]
 LDCM0324  AC60 HCT 116 C111(0.72)  LDD0641  [7]
 LDCM0325  AC61 HCT 116 C111(1.00)  LDD0642  [7]
 LDCM0326  AC62 HCT 116 C111(0.53)  LDD0643  [7]
 LDCM0327  AC63 HCT 116 C111(0.73)  LDD0644  [7]
 LDCM0328  AC64 HCT 116 C111(0.58)  LDD0645  [7]
 LDCM0329  AC65 HCT 116 C111(0.65)  LDD0646  [7]
 LDCM0330  AC66 HCT 116 C111(0.73)  LDD0647  [7]
 LDCM0331  AC67 HCT 116 C111(0.34)  LDD0648  [7]
 LDCM0332  AC68 HCT 116 C111(1.19)  LDD0649  [7]
 LDCM0333  AC69 HCT 116 C111(1.22)  LDD0650  [7]
 LDCM0335  AC70 HCT 116 C111(0.79)  LDD0652  [7]
 LDCM0336  AC71 HCT 116 C111(0.86)  LDD0653  [7]
 LDCM0337  AC72 HCT 116 C111(0.98)  LDD0654  [7]
 LDCM0338  AC73 HCT 116 C111(1.13)  LDD0655  [7]
 LDCM0339  AC74 HCT 116 C111(1.33)  LDD0656  [7]
 LDCM0340  AC75 HCT 116 C111(2.15)  LDD0657  [7]
 LDCM0341  AC76 HCT 116 C111(1.67)  LDD0658  [7]
 LDCM0342  AC77 HCT 116 C111(1.11)  LDD0659  [7]
 LDCM0343  AC78 HCT 116 C111(1.55)  LDD0660  [7]
 LDCM0344  AC79 HCT 116 C111(1.17)  LDD0661  [7]
 LDCM0346  AC80 HCT 116 C111(1.52)  LDD0663  [7]
 LDCM0347  AC81 HCT 116 C111(0.17)  LDD0664  [7]
 LDCM0348  AC82 HCT 116 C111(1.81)  LDD0665  [7]
 LDCM0349  AC83 HCT 116 C111(1.02)  LDD0666  [7]
 LDCM0350  AC84 HCT 116 C111(1.30)  LDD0667  [7]
 LDCM0351  AC85 HCT 116 C111(1.64)  LDD0668  [7]
 LDCM0352  AC86 HCT 116 C111(1.24)  LDD0669  [7]
 LDCM0353  AC87 HCT 116 C111(1.32)  LDD0670  [7]
 LDCM0354  AC88 HCT 116 C111(1.43)  LDD0671  [7]
 LDCM0355  AC89 HCT 116 C111(1.22)  LDD0672  [7]
 LDCM0357  AC90 HCT 116 C111(1.59)  LDD0674  [7]
 LDCM0358  AC91 HCT 116 C111(1.09)  LDD0675  [7]
 LDCM0359  AC92 HCT 116 C111(1.23)  LDD0676  [7]
 LDCM0360  AC93 HCT 116 C111(1.36)  LDD0677  [7]
 LDCM0361  AC94 HCT 116 C111(1.43)  LDD0678  [7]
 LDCM0362  AC95 HCT 116 C111(1.49)  LDD0679  [7]
 LDCM0363  AC96 HCT 116 C111(1.38)  LDD0680  [7]
 LDCM0364  AC97 HCT 116 C111(1.20)  LDD0681  [7]
 LDCM0365  AC98 HCT 116 C111(0.45)  LDD0682  [7]
 LDCM0366  AC99 HCT 116 C111(1.01)  LDD0683  [7]
 LDCM0356  AKOS034007680 HEK-293T C111(1.10)  LDD1570  [21]
 LDCM0156  Aniline NCI-H1299 12.05  LDD0403  [2]
 LDCM0630  CCW28-3 231MFP C111(1.52)  LDD2214  [22]
 LDCM0371  CL102 HEK-293T C111(0.95)  LDD1575  [21]
 LDCM0374  CL105 HCT 116 C111(1.13)  LDD0691  [7]
 LDCM0375  CL106 HCT 116 C111(0.89)  LDD0692  [7]
 LDCM0376  CL107 HCT 116 C111(0.89)  LDD0693  [7]
 LDCM0377  CL108 HCT 116 C111(0.85)  LDD0694  [7]
 LDCM0378  CL109 HCT 116 C111(1.09)  LDD0695  [7]
 LDCM0380  CL110 HCT 116 C111(0.98)  LDD0697  [7]
 LDCM0381  CL111 HCT 116 C111(1.28)  LDD0698  [7]
 LDCM0384  CL114 HEK-293T C111(1.06)  LDD1588  [21]
 LDCM0387  CL117 HCT 116 C111(0.51)  LDD0704  [7]
 LDCM0388  CL118 HCT 116 C111(0.69)  LDD0705  [7]
 LDCM0389  CL119 HCT 116 C111(0.86)  LDD0706  [7]
 LDCM0391  CL120 HCT 116 C111(0.77)  LDD0708  [7]
 LDCM0392  CL121 HCT 116 C111(0.96)  LDD0709  [7]
 LDCM0393  CL122 HCT 116 C111(1.01)  LDD0710  [7]
 LDCM0394  CL123 HCT 116 C111(0.74)  LDD0711  [7]
 LDCM0395  CL124 HCT 116 C111(0.76)  LDD0712  [7]
 LDCM0396  CL125 HCT 116 C111(0.71)  LDD0713  [7]
 LDCM0397  CL126 HCT 116 C111(0.68)  LDD0714  [7]
 LDCM0398  CL127 HCT 116 C111(1.16)  LDD0715  [7]
 LDCM0399  CL128 HCT 116 C111(0.70)  LDD0716  [7]
 LDCM0401  CL14 HEK-293T C111(0.86)  LDD1605  [21]
 LDCM0404  CL17 HEK-293T C111(1.03)  LDD1608  [21]
 LDCM0407  CL2 HEK-293T C111(0.84)  LDD1611  [21]
 LDCM0414  CL26 HEK-293T C111(1.01)  LDD1618  [21]
 LDCM0417  CL29 HEK-293T C111(1.09)  LDD1621  [21]
 LDCM0431  CL41 HEK-293T C111(1.01)  LDD1635  [21]
 LDCM0436  CL46 HCT 116 C111(1.17)  LDD0753  [7]
 LDCM0437  CL47 HCT 116 C111(1.98)  LDD0754  [7]
 LDCM0438  CL48 HCT 116 C111(0.99)  LDD0755  [7]
 LDCM0439  CL49 HCT 116 C111(1.94)  LDD0756  [7]
 LDCM0440  CL5 HEK-293T C111(1.19)  LDD1644  [21]
 LDCM0441  CL50 HCT 116 C111(0.88)  LDD0758  [7]
 LDCM0442  CL51 HCT 116 C111(0.80)  LDD0759  [7]
 LDCM0443  CL52 HCT 116 C111(0.97)  LDD0760  [7]
 LDCM0444  CL53 HCT 116 C111(0.84)  LDD0761  [7]
 LDCM0445  CL54 HCT 116 C111(1.31)  LDD0762  [7]
 LDCM0446  CL55 HCT 116 C111(1.88)  LDD0763  [7]
 LDCM0447  CL56 HCT 116 C111(0.62)  LDD0764  [7]
 LDCM0448  CL57 HCT 116 C111(1.22)  LDD0765  [7]
 LDCM0449  CL58 HCT 116 C111(1.22)  LDD0766  [7]
 LDCM0450  CL59 HCT 116 C111(0.80)  LDD0767  [7]
 LDCM0452  CL60 HCT 116 C111(1.14)  LDD0769  [7]
 LDCM0454  CL62 HEK-293T C111(1.03)  LDD1657  [21]
 LDCM0457  CL65 HEK-293T C111(1.07)  LDD1660  [21]
 LDCM0467  CL74 HEK-293T C111(0.97)  LDD1670  [21]
 LDCM0470  CL77 HEK-293T C111(1.00)  LDD1673  [21]
 LDCM0480  CL86 HEK-293T C111(0.88)  LDD1683  [21]
 LDCM0483  CL89 HEK-293T C111(1.05)  LDD1686  [21]
 LDCM0493  CL98 HEK-293T C111(0.82)  LDD1696  [21]
 LDCM0175  Ethacrynic acid HeLa C111(1.08); C111(1.10)  LDD2210  [6]
 LDCM0427  Fragment51 HEK-293T C111(0.97)  LDD1631  [21]
 LDCM0022  KB02 A101D C111(1.36)  LDD2250  [23]
 LDCM0023  KB03 A101D C111(1.80)  LDD2667  [23]
 LDCM0024  KB05 HMCB C111(1.49)  LDD3312  [23]
 LDCM0628  OTUB2-COV-1 HEK-293T C111(0.81)  LDD2207  [24]

The Interaction Atlas With This Target

The Protein(s) Related To This Target

Enzyme
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
DNA (cytosine-5)-methyltransferase 3A (DNMT3A) C5-methyltransferase family Q9Y6K1
Other
Click To Hide/Show 7 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Histone chaperone ASF1B (ASF1B) ASF1 family Q9NVP2
Chromatin assembly factor 1 subunit A (CHAF1A) CHAF1A family Q13111
Death domain-associated protein 6 (DAXX) DAXX family Q9UER7
Histone H4 (H4C1; H4C2; H4C3; H4C4; H4C5; H4C6; H4C8; H4C9; H4C11; H4C12; H4C13; H4C14; H4C15; H4C16) Histone H4 family P62805
Proline-, glutamic acid- and leucine-rich protein 1 (PELP1) RIX1/PELP1 family Q8IZL8
Transcription initiation factor TFIID subunit 3 (TAF3) TAF3 family Q5VWG9
Chromobox protein homolog 5 (CBX5) . P45973

References

1 Labeling Preferences of Diazirines with Protein Biomolecules. J Am Chem Soc. 2021 May 5;143(17):6691-6700. doi: 10.1021/jacs.1c02509. Epub 2021 Apr 20.
Mass spectrometry data entry: PXD025140
2 Quantitative and Site-Specific Chemoproteomic Profiling of Targets of Acrolein. Chem Res Toxicol. 2019 Mar 18;32(3):467-473. doi: 10.1021/acs.chemrestox.8b00343. Epub 2019 Jan 15.
3 Chemoproteomic profiling of kinases in live cells using electrophilic sulfonyl triazole probes. Chem Sci. 2021 Jan 21;12(9):3295-3307. doi: 10.1039/d0sc06623k.
4 A Paal-Knorr agent for chemoproteomic profiling of targets of isoketals in cells. Chem Sci. 2021 Oct 15;12(43):14557-14563. doi: 10.1039/d1sc02230j. eCollection 2021 Nov 10.
Mass spectrometry data entry: PXD028270
5 2H-Azirine-Based Reagents for Chemoselective Bioconjugation at Carboxyl Residues Inside Live Cells. J Am Chem Soc. 2020 Apr 1;142(13):6051-6059. doi: 10.1021/jacs.9b12116. Epub 2020 Mar 23.
6 Chemoproteomic Profiling Reveals Ethacrynic Acid Targets Adenine Nucleotide Translocases to Impair Mitochondrial Function. Mol Pharm. 2018 Jun 4;15(6):2413-2422. doi: 10.1021/acs.molpharmaceut.8b00250. Epub 2018 May 15.
7 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.
8 Targeted Proteomic Approaches for Proteome-Wide Characterizations of the AMP-Binding Capacities of Kinases. J Proteome Res. 2022 Aug 5;21(8):2063-2070. doi: 10.1021/acs.jproteome.2c00225. Epub 2022 Jul 12.
9 Tunable Amine-Reactive Electrophiles for Selective Profiling of Lysine. Angew Chem Int Ed Engl. 2022 Jan 26;61(5):e202112107. doi: 10.1002/anie.202112107. Epub 2021 Dec 16.
10 Enhancing Cysteine Chemoproteomic Coverage through Systematic Assessment of Click Chemistry Product Fragmentation. Anal Chem. 2022 Mar 8;94(9):3800-3810. doi: 10.1021/acs.analchem.1c04402. Epub 2022 Feb 23.
Mass spectrometry data entry: PXD028853
11 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
12 Comparison of Quantitative Mass Spectrometry Platforms for Monitoring Kinase ATP Probe Uptake in Lung Cancer. J Proteome Res. 2018 Jan 5;17(1):63-75. doi: 10.1021/acs.jproteome.7b00329. Epub 2017 Nov 22.
Mass spectrometry data entry: PXD006095 , PXD006096
13 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
14 Benchmarking Cleavable Biotin Tags for Peptide-Centric Chemoproteomics. J Proteome Res. 2022 May 6;21(5):1349-1358. doi: 10.1021/acs.jproteome.2c00174. Epub 2022 Apr 25.
Mass spectrometry data entry: PXD031019
15 Solid Phase Synthesis of Fluorosulfate Containing Macrocycles for Chemoproteomic Workflows. bioRxiv [Preprint]. 2023 Feb 18:2023.02.17.529022. doi: 10.1101/2023.02.17.529022.
Mass spectrometry data entry: PXD039931
16 Chemoproteomic profiling of targets of lipid-derived electrophiles by bioorthogonal aminooxy probe. Redox Biol. 2017 Aug;12:712-718. doi: 10.1016/j.redox.2017.04.001. Epub 2017 Apr 5.
17 Global targeting of functional tyrosines using sulfur-triazole exchange chemistry. Nat Chem Biol. 2020 Feb;16(2):150-159. doi: 10.1038/s41589-019-0404-5. Epub 2019 Nov 25.
18 Large-scale chemoproteomics expedites ligand discovery and predicts ligand behavior in cells. Science. 2024 Apr 26;384(6694):eadk5864. doi: 10.1126/science.adk5864. Epub 2024 Apr 26.
Mass spectrometry data entry: PXD041587
19 Design and synthesis of minimalist terminal alkyne-containing diazirine photo-crosslinkers and their incorporation into kinase inhibitors for cell- and tissue-based proteome profiling. Angew Chem Int Ed Engl. 2013 Aug 12;52(33):8551-6. doi: 10.1002/anie.201300683. Epub 2013 Jun 10.
20 Small Molecule Interactome Mapping by Photoaffinity Labeling Reveals Binding Site Hotspots for the NSAIDs. J Am Chem Soc. 2018 Mar 28;140(12):4259-4268. doi: 10.1021/jacs.7b11639. Epub 2018 Mar 15.
Mass spectrometry data entry: PXD007094
21 Accelerating multiplexed profiling of protein-ligand interactions: High-throughput plate-based reactive cysteine profiling with minimal input. Cell Chem Biol. 2024 Mar 21;31(3):565-576.e4. doi: 10.1016/j.chembiol.2023.11.015. Epub 2023 Dec 19.
Mass spectrometry data entry: PXD044402
22 Covalent Ligand Screening Uncovers a RNF4 E3 Ligase Recruiter for Targeted Protein Degradation Applications. ACS Chem Biol. 2019 Nov 15;14(11):2430-2440. doi: 10.1021/acschembio.8b01083. Epub 2019 May 13.
23 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
24 Rapid Covalent-Probe Discovery by Electrophile-Fragment Screening. J Am Chem Soc. 2019 Jun 5;141(22):8951-8968. doi: 10.1021/jacs.9b02822. Epub 2019 May 22.