Target Binding Site Detail
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T56545 | Target Info | |||
| Target Name | Apolipoprotein A-I (APOA1) | ||||
| Synonyms | Truncated apolipoprotein AI; Apolipoprotein A1; ApoAI; ApoA-I; Apo-AI | ||||
| Target Type | Clinical trial Target | ||||
| Gene Name | APOA1 | ||||
| Biochemical Class | Apolipoprotein | ||||
| 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: 2MSC NMR data-driven model of GTPase KRas-GDP tethered to a lipid-bilayer nanodisc | ||||||
| Method | Solution NMR | Resolution | N.A. | Mutation | No | [1] |
| PDB Sequence |
LKLLDNWDSV
210 TSTFSKLREQ220 LGPVTQEFWD230 NLEKETEGLR240 QEMSKDLEEV250 KAKVQPYLDD 260 FQKKWQEEME270 LYRQKVEPLR280 AELQEGARQK290 LHELQEKLSP300 LGEEMRDRAR 310 AHVDALRTHL320 APYSDELRQR330 LAARLEALKE340 NGGARLAEYH350 AKATEHLSTL 360 SEKAKPALED370 LRQGLLPVLE380 SFKVSFLSAL390 EEYTKKLN
|
|||||
|
|
||||||
| PDB ID: 2MSD NMR data-driven model of GTPase KRas-GNP tethered to a lipid-bilayer nanodisc | ||||||
| Method | Solution NMR | Resolution | N.A. | Mutation | No | [1] |
| PDB Sequence |
LKLLDNWDSV
210 TSTFSKLREQ220 LGPVTQEFWD230 NLEKETEGLR240 QEMSKDLEEV250 KAKVQPYLDD 260 FQKKWQEEME270 LYRQKVEPLR280 AELQEGARQK290 LHELQEKLSP300 LGEEMRDRAR 310 AHVDALRTHL320 APYSDELRQR330 LAARLEALKE340 NGGARLAEYH350 AKATEHLSTL 360 SEKAKPALED370 LRQGLLPVLE380 SFKVSFLSAL390 EEYTKKLN
|
|||||
|
|
||||||
| 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 | [2] |
| PDB Sequence |
LKLLDNWDSV
210 TSTFSKLREQ220 LGPVTQEFWD230 NLEKETEGLR240 QEMSKDLEEV250 KAKVQPYLDD 260 FQKKWQEEME270 LYRQKVEPLR280 AELQEGARQK290 LHELQEKLSP300 LGEEMRDRAR 310 AHVDALRTHL320 APYSDELRQR330 LAARLEALKE340 NGGARLAEYH350 AKATEHLSTL 360 SEKAKPALED370 LRQGLLPVLE380 SFKVSFLSAL390 EEYTKKLN
|
|||||
|
|
||||||
| 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 | [2] |
| PDB Sequence |
LKLLDNWDSV
210 TSTFSKLREQ220 LGPVTQEFWD230 NLEKETEGLR240 QEMSKDLEEV250 KAKVQPYLDD 260 FQKKWQEEME270 LYRQKVEPLR280 AELQEGARQK290 LHELQEKLSP300 LGEEMRDRAR 310 AHVDALRTHL320 APYSDELRQR330 LAARLEALKE340 NGGARLAEYH350 AKATEHLSTL 360 SEKAKPALED370 LRQGLLPVLE380 SFKVSFLSAL390 EEYTKKLN
|
|||||
|
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:371 or .A:375 or .A:386; 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 |
LKLLDNWDSV
210 TSTFSKLREQ220 LGPVTQEFWD230 NLEKETEGLR240 QEMSKDLEEV250 KAKVQPYLDD 260 FQKKWQEEME270 LYRQKVEPLR280 AELQEGARQK290 LHELQEKLSP300 LGEEMRDRAR 310 AHVDALRTHL320 APYSDELRQR330 LAARLEALKE340 NGGARLAEYH350 AKATEHLSTL 360 SEKAKPALED370 LRQGLLPVLE380 SFKVSFLSAL390 EEYTKKLN
|
|||||
|
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:368 or .A:371 or .A:375 or .A:382 or .A:386; 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 |
STFSKLREQL
264 GPVTQEFWDN274 LEKETEGLRQ284 EMSKDLEEVK294 AKVQPYLDDF304 QKKWQEEMEL 314 YRQKVEPLRA324 ELQEGARQKL334 HELQEKLSPL344 GEEMRDRARA354 HVDALRTHLA 364 PYSDELRQRL374 AARLEALKEN384 GGARLAEYHA394 KATEHLSTLS404 EKAKPALEDL 414 RQGLLPVLES424 FKVSFLSALE434 EYTKKLN
|
|||||
|
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 .D:269 or .D:270 or .D:272 or .D:273 or .D:276 or .D:305 or .D:306 or .D:309 or .D:312 or .D:327 or .D:330 or .D:429 or .D:430 or .D:433 or .D:440 or .D:441; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
||||||
| 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 | [5] |
| PDB Sequence |
LKLLDNWDSV
210 TSTFSKLREQ220 LGPVTQEFWD230 NLEKETEGLR240 QEMSKDLEEV250 KAKVQPYLDD 260 FQKKWQEEME270 LYRQKVEPLR280 AELQEGARQK290 LHELQEKLSP300 LGEEMRDRAR 310 AHVDALRTHL320 APYSDELRQR330 LAARLEALKE340 NGGARLAEYH350 AKATEHLSTL 360 SEKAKPALED370 LRQGLLPVLE380 SFKVSFLSAL390 EEYTKKLN
|
|||||
|
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:368; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
||||||
| PDB ID: 6PTW NMR data-driven model of KRas-GMPPNP:RBD-CRD complex tethered to a nanodisc (state B) | ||||||
| Method | Solution NMR | Resolution | N.A. | Mutation | No | [5] |
| PDB Sequence |
LKLLDNWDSV
210 TSTFSKLREQ220 LGPVTQEFWD230 NLEKETEGLR240 QEMSKDLEEV250 KAKVQPYLDD 260 FQKKWQEEME270 LYRQKVEPLR280 AELQEGARQK290 LHELQEKLSP300 LGEEMRDRAR 310 AHVDALRTHL320 APYSDELRQR330 LAARLEALKE340 NGGARLAEYH350 AKATEHLSTL 360 SEKAKPALED370 LRQGLLPVLE380 SFKVSFLSAL390 EEYTKKLN
|
|||||
|
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:368 or .A:371 or .A:372 or .A:375; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
||||||
| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Oncogenic and RASopathy-associated K-RAS mutations relieve membrane-dependent occlusion of the effector-binding site. Proc Natl Acad Sci U S A. 2015 May 26;112(21):6625-30. | ||||
| REF 2 | 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 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. | ||||
| REF 5 | 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. | ||||
If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.