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 T60631 Target Info
Target Name Proto-oncogene c-Ret (RET)
Synonyms RET51; RET receptor tyrosine kinase; RET mutant Y791F; RET mutant V804M; RET mutant V804L; RET mutant S891A; RET mutant M918T; RET mutant G691S; Proto-oncogene tyrosine-protein kinase receptor Ret; PTC; Cadherin family member 12; CDHR16; CDHF12; C-ret
Target Type Successful Target
Gene Name RET
Biochemical Class Kinase
UniProt ID
RET_HUMAN
Ligand General Information  Top
Ligand Name Adenosine monophosphate Ligand Info
Canonical SMILES C1=NC(=C2C(=N1)N(C=N2)C3C(C(C(O3)COP(=O)(O)O)O)O)N
InChI 1S/C10H14N5O7P/c11-8-5-9(13-2-12-8)15(3-14-5)10-7(17)6(16)4(22-10)1-21-23(18,19)20/h2-4,6-7,10,16-17H,1H2,(H2,11,12,13)(H2,18,19,20)/t4-,6-,7-,10-/m1/s1
InChIKey UDMBCSSLTHHNCD-KQYNXXCUSA-N
PubChem Compound ID 6083
Drug Binding Sites of Target  Top
PDB ID: 6NE7      Structure of G810A mutant of RET protein tyrosine kinase domain.
Method X-ray diffraction Resolution 1.99 Å Mutation Yes [1]
PDB Sequence
GPLSLSVDAF
709
KILEDPKWEF
719
PRKNLVLGKT
729
LGEGEFGKVV
739
KATAFHLKGR
749

AGYTTVAVKM
759
LKENASPSEL
769
RDLLSEFNVL
779
KQVNHPHVIK
789
LYGACSQDGP
799

LLLIVEYAKY
809
ASLRGFLRES
819
RKVGERALTM
848
GDLISFAWQI
858
SQGMQYLAEM
868

KLVHRDLAAR
878
NILVAEGRKM
888
KISDFGLSRD
898
VEEDSVKRSQ
910
GRIPVKWMAI
920

ESLFDHIYTT
930
QSDVWSFGVL
940
LWEIVTLGGN
950
PYPGIPPERL
960
FNLLKTGHRM
970

ERPDNCSEEM
980
YRLMLQCWKQ
990
EPDKRPVFAD
1000
ISKDLEKMMV
1010
KRR
Residue
Distance (Å)
LEU730
3.694
VAL738
3.341
ALA756
3.433
ILE788
4.265
VAL804
3.606
Residue
Distance (Å)
GLU805
2.739
TYR806
3.428
ALA807
2.877
ALA810
4.317
LEU881
3.320
PDB ID: 2IVT      Crystal structure of phosphorylated RET tyrosine kinase domain
Method X-ray diffraction Resolution 2.60 Å Mutation No [2]
PDB Sequence
GPLSLSVDAF
709
KIPKWEFPRK
722
NLVLGKTLGE
732
GEFGKVVKAT
742
AFHLKGRAGY
752

TTVAVKMLKE
762
NASPSELRDL
772
LSEFNVLKQV
782
NHPHVIKLYG
792
ACSQDGPLLL
802

IVEYAKYGSL
812
RGFLRESRKV
822
RALTMGDLIS
853
FAWQISQGMQ
863
YLAEMKLVHR
873

DLAARNILVA
883
EGRKMKISDF
893
GLSRDVYEED
903
SVKRSQGRIP
914
VKWMAIESLF
924

DHIYTTQSDV
934
WSFGVLLWEI
944
VTLGGNPYPG
954
IPPERLFNLL
964
KTGHRMERPD
974

NCSEEMYRLM
984
LQCWKQEPDK
994
RPVFADISKD
1004
LEKMMVKR
Residue
Distance (Å)
LEU730
3.697
GLY731
3.647
GLU732
3.690
GLY733
3.312
GLU734
4.823
GLY736
3.973
VAL738
3.593
ALA756
3.409
LYS758
2.823
GLU775
4.957
ILE788
4.153
Residue
Distance (Å)
VAL804
3.779
GLU805
2.801
TYR806
4.021
ALA807
3.289
GLY810
4.494
SER811
3.972
ARG878
3.128
ASN879
3.439
LEU881
3.517
SER891
4.317
ASP892
3.588
References  Top
REF 1 Structural basis of resistance of mutant RET protein-tyrosine kinase to its inhibitors nintedanib and vandetanib. J Biol Chem. 2019 Jul 5;294(27):10428-10437.
REF 2 Structure and chemical inhibition of the RET tyrosine kinase domain. J Biol Chem. 2006 Nov 3;281(44):33577-87.

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