Target Binding Site Detail
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T48598 | Target Info | |||
| Target Name | GTPase KRas (KRAS) | ||||
| Synonyms | c-Ki-ras; c-K-ras; RASK2; Ki-Ras; KRAS2; K-Ras 2 | ||||
| Target Type | Clinical trial Target | ||||
| Gene Name | KRAS | ||||
| Biochemical Class | Small GTPase | ||||
| UniProt ID | |||||
| Ligand General Information | Top | ||||
|---|---|---|---|---|---|
| Ligand Name | [(2S)-2-azaniumyl-2-carboxyethyl] [(2R)-2,3-bis[[(Z)-octadec-9-enoyl]oxy]propyl] phosphate | Ligand Info | |||
| Canonical SMILES | CCCCCCCCC=CCCCCCCCC(=O)OCC(COP(=O)([O-])OCC(C(=O)O)[NH3+])OC(=O)CCCCCCCC=CCCCCCCCC | ||||
| InChI | 1S/C42H78NO10P/c1-3-5-7-9-11-13-15-17-19-21-23-25-27-29-31-33-40(44)50-35-38(36-51-54(48,49)52-37-39(43)42(46)47)53-41(45)34-32-30-28-26-24-22-20-18-16-14-12-10-8-6-4-2/h17-20,38-39H,3-16,21-37,43H2,1-2H3,(H,46,47)(H,48,49)/b19-17-,20-18-/t38-,39+/m1/s1 | ||||
| InChIKey | WTBFLCSPLLEDEM-JIDRGYQWSA-N | ||||
| PubChem Compound ID | 44825325 | ||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| PDB ID: 6CC9 NMR data-driven model of GTPase KRas-GMPPNP:Cmpd2 complex tethered to a nanodisc | ||||||
| Method | Solution NMR | Resolution | N.A. | Mutation | Yes | [1] |
| PDB Sequence |
MTEYKLVVVG
10 AVGVGKSALT20 IQLIQNHFVD30 EYDPTIEDSY40 RKQVVIDGET50 CLLDILDTAG 60 QEEYSAMRDQ70 YMRTGEGFLC80 VFAINNTKSF90 EDIHHYREQI100 KRVKDSEDVP 110 MVLVGNKCDL120 PSRTVDTKQA130 QDLARSYGIP140 FIETSAKTRQ150 GVDDAFYTLV 160 REIRKHKEKM170 SKDGKKKKKK180 SKTKC
|
|||||
|
|
||||||
| PDB ID: 6CCH NMR data-driven model of GTPase KRas-GMPPNP tethered to a nanodisc (E3 state) | ||||||
| Method | Solution NMR | Resolution | N.A. | Mutation | Yes | [1] |
| PDB Sequence |
MTEYKLVVVG
10 AVGVGKSALT20 IQLIQNHFVD30 EYDPTIEDSY40 RKQVVIDGET50 CLLDILDTAG 60 QEEYSAMRDQ70 YMRTGEGFLC80 VFAINNTKSF90 EDIHHYREQI100 KRVKDSEDVP 110 MVLVGNKCDL120 PSRTVDTKQA130 QDLARSYGIP140 FIETSAKTRQ150 GVDDAFYTLV 160 REIRKHKEKM170 SKDGKKKKKK180 SKTKC
|
|||||
|
|
||||||
| PDB ID: 6CCX NMR data-driven model of GTPase KRas-GMPPNP:Cmpd2 complex tethered to a nanodisc | ||||||
| Method | Solution NMR | Resolution | N.A. | Mutation | Yes | [1] |
| PDB Sequence |
MTEYKLVVVG
10 AVGVGKSALT20 IQLIQNHFVD30 EYDPTIEDSY40 RKQVVIDGET50 CLLDILDTAG 60 QEEYSAMRDQ70 YMRTGEGFLC80 VFAINNTKSF90 EDIHHYREQI100 KRVKDSEDVP 110 MVLVGNKCDL120 PSRTVDTKQA130 QDLARSYGIP140 FIETSAKTRQ150 GVDDAFYTLV 160 REIRKHKEKM170 SKDGKKKKKK180 SKTKC
|
|||||
|
|
||||||
| PDB ID: 6PTS NMR data-driven model of KRas-GMPPNP:RBD-CRD complex tethered to a nanodisc (state A) | ||||||
| Method | Solution NMR | Resolution | N.A. | Mutation | No | [2] |
| PDB Sequence |
MTEYKLVVVG
10 AGGVGKSALT20 IQLIQNHFVD30 EYDPTIEDSY40 RKQVVIDGET50 CLLDILDTAG 60 QEEYSAMRDQ70 YMRTGEGFLC80 VFAINNTKSF90 EDIHHYREQI100 KRVKDSEDVP 110 MVLVGNKCDL120 PSRTVDTKQA130 QDLARSYGIP140 FIETSAKTRQ150 GVDDAFYTLV 160 REIRKHKEKM170 SKDGKKKKKK180 SKTKC
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .17F or .17F2 or .17F3 or :317F;style chemicals stick;color identity;select .B:165 or .B:168 or .B:169 or .B:172 or .B:142 or .B:143 or .B:151 or .B:154 or .B:155 or .B:158 or .B:161 or .B:168; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
||||||
| PDB ID: 6W4E NMR-driven structure of KRAS4B-GTP homodimer on a lipid bilayer nanodisc | ||||||
| Method | Solution NMR | Resolution | N.A. | Mutation | No | [3] |
| PDB Sequence |
STEYKLVVVG
10 ADGVGKSALT20 IQLIQNHFVD30 EYDPTIEDSY40 RKQVVIDGET50 CLLDILDTAG 60 QEEYSAMRDQ70 YMRTGEGFLC80 VFAINNTKSF90 EDIHHYREQI100 KRVKDSEDVP 110 MVLVGNKCDL120 PSRTVDTKQA130 QDLARSYGIP140 FIETSAKTRQ150 GVDDAFYTLV 160 REIRKHKEKM170 SKDGKKKKKK180 SKTK
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .17F or .17F2 or .17F3 or :317F;style chemicals stick;color identity;select .B:178 or .B:179 or .B:180 or .B:181 or .B:182; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
||||||
| PDB ID: 7RSE NMR-driven structure of the KRAS4B-G12D "alpha-beta" dimer on a lipid bilayer nanodisc | ||||||
| Method | Solution NMR | Resolution | N.A. | Mutation | Yes | [4] |
| PDB Sequence |
TEYKLVVVGA
11 DGVGKSALTI21 QLIQNHFVDE31 YDPTIEDSYR41 KQVVIDGETC51 LLDILDTAGQ 61 EEYSAMRDQY71 MRTGEGFLCV81 FAINNTKSFE91 DIHHYREQIK101 RVKDSEDVPM 111 VLVGNKCDLP121 SRTVDTKQAQ131 DLARSYGIPF141 IETSAKTRQG151 VDDAFYTLVR 161 EIRKHKEKMS171 KDGKKKKKKS181 KTK
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .17F or .17F2 or .17F3 or :317F;style chemicals stick;color identity;select .A:176; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
||||||
| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Inhibition of K-RAS4B by a Unique Mechanism of Action: Stabilizing Membrane-Dependent Occlusion of the Effector-Binding Site. Cell Chem Biol. 2018 Nov 15;25(11):1327-1336.e4. | ||||
| REF 2 | Multivalent assembly of KRAS with the RAS-binding and cysteine-rich domains of CRAF on the membrane. Proc Natl Acad Sci U S A. 2020 Jun 2;117(22):12101-12108. | ||||
| REF 3 | Two Distinct Structures of Membrane-Associated Homodimers of GTP- and GDP-Bound KRAS4B Revealed by Paramagnetic Relaxation Enhancement. Angew Chem Int Ed Engl. 2020 Jun 26;59(27):11037-11045. | ||||
| REF 4 | Oncogenic KRAS G12D mutation promotes dimerization through a second, phosphatidylserine-dependent interface: a model for KRAS oligomerization. Chem Sci. 2021 Sep 7;12(38):12827-12837. | ||||
If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.