Target Binding Site Detail

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Target General Information
Ligand General Information
Drug Binding Sites of Target
References
Target General Information  Top
Target ID T75243 Target Info
Target Name Serine/threonine-protein kinase mTOR (mTOR)
Synonyms Target of rapamycin; TOR kinase; Rapamycin target protein 1; Rapamycin target protein; Rapamycin and FKBP12 target 1; RAPT1; RAFT1; Mechanistic target of rapamycin; Mammalian target of rapamycin; FRAP2; FRAP1; FRAP; FKBP12-rapamycin complex-associated protein; FKBP-rapamycin associated protein; FK506-binding protein 12-rapamycin complex-associated protein 1
Target Type Successful Target
Gene Name MTOR
Biochemical Class Kinase
UniProt ID
MTOR_HUMAN
Ligand General Information  Top
Ligand Name Sirolimus Ligand Info
Canonical SMILES CC1CCC2CC(C(=CC=CC=CC(CC(C(=O)C(C(C(=CC(C(=O)CC(OC(=O)C3CCCCN3C(=O)C(=O)C1(O2)O)C(C)CC4CCC(C(C4)OC)O)C)C)O)OC)C)C)C)OC
InChI 1S/C51H79NO13/c1-30-16-12-11-13-17-31(2)42(61-8)28-38-21-19-36(7)51(60,65-38)48(57)49(58)52-23-15-14-18-39(52)50(59)64-43(33(4)26-37-20-22-40(53)44(27-37)62-9)29-41(54)32(3)25-35(6)46(56)47(63-10)45(55)34(5)24-30/h11-13,16-17,25,30,32-34,36-40,42-44,46-47,53,56,60H,14-15,18-24,26-29H2,1-10H3/b13-11+,16-12+,31-17+,35-25+/t30-,32-,33-,34-,36-,37+,38+,39+,40-,42+,43+,44-,46-,47+,51-/m1/s1
InChIKey QFJCIRLUMZQUOT-HPLJOQBZSA-N
PubChem Compound ID 5284616
Drug Binding Sites of Target  Top
PDB ID: 4DRI      Co-crystal structure of the PPIase domain of FKBP51, Rapamycin and the FRB fragment of mTOR
Method X-ray diffraction Resolution 1.45 Å Mutation No [1]
PDB Sequence
GAMDPEFMEM
2026
WHEGLEEASR
2036
LYFGERNVKG
2046
MFEVLEPLHA
2056
MMERGPQTLK
2066

ETSFNQAYGR
2076
DLMEAQEWCR
2086
KYMKSGNVKD
2096
LTQAWDLYYH
2106
VFRRIS
Residue
Distance (Å)
LEU2031
3.600
GLU2032
3.770
SER2035
3.419
ARG2036
3.984
PHE2039
3.534
GLY2040
4.222
Residue
Distance (Å)
THR2098
3.475
TRP2101
3.754
ASP2102
3.131
TYR2105
3.679
PHE2108
3.456
PDB ID: 4DRJ      o-crystal structure of the PPIase domain of FKBP52, Rapamycin and the FRB fragment of mTOR
Method X-ray diffraction Resolution 1.80 Å Mutation No [1]
PDB Sequence
MDPEFMEMWH
2028
EGLEEASRLY
2038
FGERNVKGMF
2048
EVLEPLHAMM
2058
ERGPQTLKET
2068

SFNQAYGRDL
2078
MEAQEWCRKY
2088
MKSGNVKDLT
2098
QAWDLYYHVF
2108
RRISKQ
Residue
Distance (Å)
LEU2031
3.644
GLU2032
3.465
SER2035
3.355
ARG2036
4.061
PHE2039
3.446
GLY2040
4.373
Residue
Distance (Å)
THR2098
3.356
TRP2101
3.718
ASP2102
3.345
TYR2105
3.362
PHE2108
3.423
PDB ID: 4DRH      Co-crystal structure of the PPIase domain of FKBP51, Rapamycin and the FRB fragment of mTOR at low pH
Method X-ray diffraction Resolution 2.30 Å Mutation No [1]
PDB Sequence
AMDPEFMEMW
2027
HEGLEEASRL
2037
YFGERNVKGM
2047
FEVLEPLHAM
2057
MERGPQTLKE
2067

TSFNQAYGRD
2077
LMEAQEWCRK
2087
YMKSGNVKDL
2097
TQAWDLYYHV
2107
FRRIS
Residue
Distance (Å)
LEU2031
3.636
GLU2032
4.243
SER2035
3.377
ARG2036
3.743
PHE2039
3.474
LEU2097
4.964
Residue
Distance (Å)
THR2098
3.171
TRP2101
3.684
ASP2102
3.484
TYR2105
3.592
PHE2108
3.662
PDB ID: 6M4U      Crystal structure of FKBP-FRB T2098L mutant in complex with rapamycin
Method X-ray diffraction Resolution 2.20 Å Mutation Yes [2]
PDB Sequence
ILWHEMWHEG
2030
LEEASRLYFG
2040
ERNVKGMFEV
2050
LEPLHAMMER
2060
GPQTLKETSF
2070

NQAYGRDLME
2080
AQEWCRKYMK
2090
SGNVKDLLQA
2100
WDLYYHVFRR
2110
ISK
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .RAP or .RAP2 or .RAP3 or :3RAP;style chemicals stick;color identity;select .B:2031 or .B:2032 or .B:2035 or .B:2036 or .B:2039 or .B:2040 or .B:2098 or .B:2101 or .B:2102 or .B:2105 or .B:2108 or .B:2109; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
LEU2031
3.599
GLU2032
3.707
SER2035
3.513
ARG2036
3.842
PHE2039
3.787
GLY2040
4.047
Residue
Distance (Å)
LEU2098
3.164
TRP2101
4.013
ASP2102
3.874
TYR2105
3.506
PHE2108
3.365
ARG2109
4.674
PDB ID: 1FAP      THE STRUCTURE OF THE IMMUNOPHILIN-IMMUNOSUPPRESSANT FKBP12-RAPAMYCIN COMPLEX INTERACTING WITH HUMAN FRAP
Method X-ray diffraction Resolution 2.70 Å Mutation No [3]
PDB Sequence
RVAILWHEMW
2027
HEGLEEASRL
2037
YFGERNVKGM
2047
FEVLEPLHAM
2057
MERGPQTLKE
2067

TSFNQAYGRD
2077
LMEAQEWCRK
2087
YMKSGNVKDL
2097
TQAWDLYYHV
2107
FRRIS
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .RAP or .RAP2 or .RAP3 or :3RAP;style chemicals stick;color identity;select .B:2031 or .B:2032 or .B:2035 or .B:2036 or .B:2039 or .B:2040 or .B:2095 or .B:2098 or .B:2101 or .B:2102 or .B:2105 or .B:2108; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
LEU2031
3.487
GLU2032
3.978
SER2035
3.149
ARG2036
3.970
PHE2039
3.291
GLY2040
3.932
Residue
Distance (Å)
LYS2095
4.346
THR2098
3.133
TRP2101
3.619
ASP2102
3.444
TYR2105
3.206
PHE2108
3.431
PDB ID: 6M4W      Crystal structure of MBP fused split FKBP-FRB T2098L mutant in complex with rapamycin
Method X-ray diffraction Resolution 3.11 Å Mutation Yes [2]
PDB Sequence
SILWHEMWHE
2029
GLEEASRLYF
2039
GERNVKGMFE
2049
VLEPLHAMME
2059
RGPQTLKETS
2069

FNQAYGRDLM
2079
EAQEWCRKYM
2089
KSGNVKDLLQ
2099
AWDLYYHVFR
2109
RIS
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .RAP or .RAP2 or .RAP3 or :3RAP;style chemicals stick;color identity;select .G:2031 or .G:2032 or .G:2035 or .G:2036 or .G:2039 or .G:2040 or .G:2098 or .G:2101 or .G:2102 or .G:2105 or .G:2108; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
LEU2031
3.498
GLU2032
4.001
SER2035
3.279
ARG2036
3.787
PHE2039
3.594
GLY2040
4.680
Residue
Distance (Å)
LEU2098
3.330
TRP2101
3.723
ASP2102
4.305
TYR2105
3.414
PHE2108
3.573
PDB ID: 5GPG      Co-crystal structure of the FK506 binding domain of human FKBP25, Rapamycin and the FRB domain of human mTOR
Method X-ray diffraction Resolution 1.67 Å Mutation No [4]
PDB Sequence
SILWHEMWHE
2029
GLEEASRLYF
2039
GERNVKGMFE
2049
VLEPLHAMME
2059
RGPQTLKETS
2069

FNQAYGRDLM
2079
EAQEWRKYMK
2090
SGNVKDLTQA
2100
WDLYYHVFRR
2110
IS
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .RAP or .RAP2 or .RAP3 or :3RAP;style chemicals stick;color identity;select .B:2031 or .B:2032 or .B:2035 or .B:2036 or .B:2039 or .B:2040 or .B:2098 or .B:2101 or .B:2102 or .B:2104 or .B:2105 or .B:2108; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
Residue
Distance (Å)
LEU2031
3.620
GLU2032
3.498
SER2035
3.232
ARG2036
3.775
PHE2039
3.569
GLY2040
4.172
Residue
Distance (Å)
THR2098
3.398
TRP2101
3.849
ASP2102
3.512
TYR2104
4.791
TYR2105
3.579
PHE2108
3.520
References  Top
REF 1 Large FK506-binding proteins shape the pharmacology of rapamycin. Mol Cell Biol. 2013 Apr;33(7):1357-67.
REF 2 Rational design and implementation of a chemically inducible heterotrimerization system. Nat Methods. 2020 Sep;17(9):928-936.
REF 3 Structure of the FKBP12-rapamycin complex interacting with the binding domain of human FRAP. Science. 1996 Jul 12;273(5272):239-42.
REF 4 Proximity-Directed Labeling Reveals a New Rapamycin-Induced Heterodimer of FKBP25 and FRB in Live Cells. ACS Cent Sci. 2016 Aug 24;2(8):506-16.

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