Target Binding Site Detail
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T03046 | Target Info | |||
| Target Name | Mutated KRAS (mKRAS) | ||||
| Synonyms | c-Ki-ras (mutated); c-K-ras (mutated); RASK2 (mutated); Ki-Ras (mutated); KRAS2 (mutated); K-Ras 2 (mutated); GTPase KRas (mutated) | ||||
| Target Type | Clinical trial Target | ||||
| Gene Name | KRAS | ||||
| UniProt ID | |||||
| Ligand General Information | Top | ||||
|---|---|---|---|---|---|
| Ligand Name | Cysteine Sulfenic Acid | Ligand Info | |||
| Canonical SMILES | C(C(C(=O)O)N)SO | ||||
| InChI | 1S/C3H7NO3S/c4-2(1-8-7)3(5)6/h2,7H,1,4H2,(H,5,6)/t2-/m0/s1 | ||||
| InChIKey | FXIRVRPOOYSARH-REOHCLBHSA-N | ||||
| PubChem Compound ID | 165339 | ||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| PDB ID: 5OCO Discovery of small molecules binding to KRAS via high affinity antibody fragment competition method. | ||||||
| Method | X-ray diffraction | Resolution | 1.66 Å | Mutation | Yes | [1] |
| PDB Sequence |
YFQGMTEYKL
6 VVVGAGGVGK16 SALTIQLIQN26 HFVDEYDPTI36 EDSYRKQVVI46 DGETLLDILD 57 TAGHEEYSAM67 RDQYMRTGEG77 FLCVFAINNT87 KSFEDIHHYR97 EQIKRVKDSE 107 DVPMVLVGNK117 CDLPSRTVDT127 KQAQDLARSY137 GIPFIETSAK147 TRQGVDDAFY 157 TLVREIRKHK167 EK
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| PDB ID: 5OCT Discovery of small molecules binding to KRAS via high affinity antibody fragment competition method. | ||||||
| Method | X-ray diffraction | Resolution | 2.07 Å | Mutation | Yes | [1] |
| PDB Sequence |
YFQGMTEYKL
6 VVVGAGGVGK16 SALTIQLIQN26 HFVDEYDPTI36 EDSYRKQVVI46 DGETLLDILD 57 TAGHEEYSAM67 RDQYMRTGEG77 FLCVFAINNT87 KSFEDIHHYR97 EQIKRVKDSE 107 DVPMVLVGNK117 CDLPSRTVDT127 KQAQDLARSY137 GIPFIETSAK147 TRQGVDDAFY 157 TLVREIRKHK167 E
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| PDB ID: 6FA1 Antibody derived (Abd-4) small molecule binding to KRAS. | ||||||
| Method | X-ray diffraction | Resolution | 1.97 Å | Mutation | Yes | [1] |
| PDB Sequence |
> Chain A
AFQGMTEYKL 6 VVVGAGGVGK16 SALTIQLIQN26 HFVDEYDPTI36 EDSYRKQVVI46 DGETLLDILD 57 TAGHEEYSAM67 RDQYMRTGEG77 FLCVFAINNT87 KSFEDIHHYR97 EQIKRVKDSE 107 DVPMVLVGNK117 CDLPSRTVDT127 KQAQDLARSY137 GIPFIETSAK147 TRQGVDDAFY 157 TLVREIRKHK167 E> Chain B AFQGMTEYKL 6 VVVGAGGVGK16 SALTIQLIQN26 HFVDEYDPTI36 EDSYRKQVVI46 DGETLLDILD 57 TAGHEEYSAM67 RDQYMRTGEG77 FLCVFAINNT87 KSFEDIHHYR97 EQIKRVKDSE 107 DVPMVLVGNK117 CDLPSRTVDT127 KQAQDLARSY137 GIPFIETSAK147 TRQGVDDAFY 157 TLVREIRKHK167 EK
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MET1[A]
4.244
THR2[A]
3.110
TYR4[A]
3.474
LYS42[A]
3.805
GLN43[A]
3.211
VAL44[A]
2.767
VAL45[A]
4.865
ILE46[A]
4.058
GLU49[A]
3.160
THR50[A]
1.321
LEU52[A]
1.309
LEU53[A]
3.900
VAL160[A]
4.272
ARG164[A]
2.533
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| PDB ID: 6FA4 Antibody derived (Abd-7) small molecule binding to KRAS. | ||||||
| Method | X-ray diffraction | Resolution | 2.02 Å | Mutation | Yes | [1] |
| PDB Sequence |
AFQGMTEYKL
6 VVVGAGGVGK16 SALTIQLIQN26 HFVDEYDPTI36 EDSYRKQVVI46 DGETLLDILD 57 TAGHEEYSAM67 RDQYMRTGEG77 FLCVFAINNT87 KSFEDIHHYR97 EQIKRVKDSE 107 DVPMVLVGNK117 CDLPSRTVDT127 KQAQDLARSY137 GIPFIETSAK147 TRQGVDDAFY 157 TLVREIRKHK167 EK
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .CSO or .CSO2 or .CSO3 or :3CSO;style chemicals stick;color identity;select .B:1 or .B:2 or .B:4 or .B:42 or .B:43 or .B:44 or .B:45 or .B:46 or .B:49 or .B:50 or .B:52 or .B:53 or .B:160 or .B:164; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 6GOM KRAS-169 Q61H GPPNHP + PPIN-1 | ||||||
| Method | X-ray diffraction | Resolution | 1.63 Å | Mutation | Yes | [2] |
| PDB Sequence |
FQGMTEYKLV
7 VVGAGGVGKS17 ALTIQLIQNH27 FVDEYDPTIE37 DSYRKQVVID47 GETLLDILDT 58 AGHEEYSAMR68 DQYMRTGEGF78 LCVFAINNTK88 SFEDIHHYRE98 QIKRVKDSED 108 VPMVLVGNKC118 DLPSRTVDTK128 QAQDLARSYG138 IPFIETSAKT148 RQGVDDAFYT 158 LVREIRKHKE168
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .CSO or .CSO2 or .CSO3 or :3CSO;style chemicals stick;color identity;select .A:1 or .A:2 or .A:4 or .A:42 or .A:43 or .A:44 or .A:45 or .A:46 or .A:49 or .A:50 or .A:52 or .A:53 or .A:160 or .A:164; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 6FA3 Antibody derived (Abd-6) small molecule binding to KRAS. | ||||||
| Method | X-ray diffraction | Resolution | 1.82 Å | Mutation | Yes | [1] |
| PDB Sequence |
AFQGMTEYKL
6 VVVGAGGVGK16 SALTIQLIQN26 HFVDEYDPTI36 EDSYRKQVVI46 DGETLLDILD 57 TAGHEEYSAM67 RDQYMRTGEG77 FLCVFAINNT87 KSFEDIHHYR97 EQIKRVKDSE 107 DVPMVLVGNK117 CDLPSRTVDT127 KQAQDLARSY137 GIPFIETSAK147 TRQGVDDAFY 157 TLVREIRKHK167 E
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .CSO or .CSO2 or .CSO3 or :3CSO;style chemicals stick;color identity;select .B:1 or .B:2 or .B:4 or .B:42 or .B:43 or .B:44 or .B:45 or .B:46 or .B:49 or .B:50 or .B:52 or .B:53 or .B:160 or .B:164; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| PDB ID: 6MQG Crystal structure of KRAS V14I-GDP demonstrating open switch 1 conformation - Form 1 | ||||||
| Method | X-ray diffraction | Resolution | 1.50 Å | Mutation | Yes | [3] |
| PDB Sequence |
EYKLVVVGAG
12 GIGKSALTIQ22 LIQNHFVDEY32 DPTIEDSYRK42 QVVIDGETCL52 LDILDTAGQE 62 EYSAMRDQYM72 RTGEGFLCVF82 AINNTKSFED92 IHHYREQIKR102 VKDSEDVPMV 112 LVGNKDLPSR123 TVDTKQAQDL133 ARSYGIPFIE143 TSAKTRQGVD153 DAFYTLVREI 163 RKHKEK
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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .CSO or .CSO2 or .CSO3 or :3CSO;style chemicals stick;color identity;select .A:84 or .A:115 or .A:116 or .A:117 or .A:119 or .A:120 or .A:123 or .A:143 or .A:144 or .A:145 or .A:148 or .A:150; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Small molecule inhibitors of RAS-effector protein interactions derived using an intracellular antibody fragment. Nat Commun. 2018 Aug 9;9(1):3169. | ||||
| REF 2 | Structure-based development of new RAS-effector inhibitors from a combination of active and inactive RAS-binding compounds. Proc Natl Acad Sci U S A. 2019 Feb 12;116(7):2545-2550. | ||||
| REF 3 | Structural basis of the atypical activation mechanism of KRAS(V14I). J Biol Chem. 2019 Sep 20;294(38):13964-13972. | ||||
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