Binding Site Information of Target
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T69128 | Target Info | |||
| Target Name | Proto-oncogene c-Ros (ROS1) | ||||
| Synonyms | c-Ros receptor tyrosine kinase; Receptor tyrosine kinase c-ros oncogene 1; ROS; Proto-oncogene tyrosine-protein kinase ROS; Proto-oncogene c-Ros-1; MCF3 | ||||
| Target Type | Successful Target | ||||
| Gene Name | ROS1 | ||||
| Biochemical Class | Kinase | ||||
| UniProt ID | |||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| Ligand Name: Crizotinib | Ligand Info | |||||
| Structure Description | Structure of Human ROS1 Kinase Domain in Complex with Crizotinib | PDB:3ZBF | ||||
| Method | X-ray diffraction | Resolution | 2.20 Å | Mutation | No | [1] |
| PDB Sequence |
IENLPAFPRE
1943 KLTLRLLLGS1953 GEVYEGTAVD1966 ILGVGSGEIK1976 VAVKTLKKGS1986 TDQEKIEFLK 1996 EAHLMSKFNH2006 PNILKQLGVC2016 LLNEPQYIIL2026 ELMEGGDLLT2036 YLRKARMATF 2046 YGPLLTLVDL2056 VDLCVDISKG2066 CVYLERMHFI2076 HRDLAARNCL2086 VSVKDYTSPR 2096 IVKIGDFGLA2106 RDIYLPVRWM2128 APESLMDGIF2138 TTQSDVWSFG2148 ILIWEILTLG 2158 HQPYPAHSNL2168 DVLNYVQTGG2178 RLEPPRNCPD2188 DLWNLMTQCW2198 AQEPDQRPTF 2208 HRIQDQLQLF2218 RNFFLNSIYK2228 SR
|
|||||
|
|
LEU1951
3.726
VAL1959
4.122
ALA1978
3.488
LYS1980
4.015
LEU2010
3.353
LEU2026
3.870
GLU2027
3.156
LEU2028
3.807
MET2029
3.038
GLU2030
4.932
|
|||||
| Ligand Name: PF-06463922 | Ligand Info | |||||
| Structure Description | Structure of Human ROS1 Kinase Domain in Complex with PF-06463922 | PDB:4UXL | ||||
| Method | X-ray diffraction | Resolution | 2.40 Å | Mutation | No | [2] |
| PDB Sequence |
IENLPAFPRE
1943 KLTLRLLLGS1953 GAFGEVYEGT1963 AVDILGVGSG1973 EIKVAVKTLK1983 KGSTDQEKIE 1993 FLKEAHLMSK2003 FNHPNILKQL2013 GVCLLNEPQY2023 IILELMEGGD2033 LLTYLRKARM 2043 ATFYGPLLTL2053 VDLVDLCVDI2063 SKGCVYLERM2073 HFIHRDLAAR2083 NCLVSVKDYT 2093 SPRIVKIGDF2103 GLARDIYKEG2121 LLPVRWMAPE2131 SLMDGIFTTQ2141 SDVWSFGILI 2151 WEILTLGHQP2161 YPAHSNLDVL2171 NYVQTGGRLE2181 PPRNCPDDLW2191 NLMTQCWAQE 2201 PDQRPTFHRI2211 QDQLQLFRNF2221 FLNSIYKSR
|
|||||
|
|
LEU1951
3.438
GLY1952
4.188
GLY1954
4.696
VAL1959
3.586
GLU1961
4.322
ALA1978
3.544
LYS1980
4.190
LEU2010
3.837
LEU2026
3.598
GLU2027
2.936
LEU2028
3.523
|
|||||
| Ligand Name: (2R)-2-[5-(6-amino-5-{(1R)-1-[2-(1,3-dihydro-2H-1,2,3-triazol-2-yl)-5-fluorophenyl]ethoxy}pyridin-3-yl)-4-methyl-1,3-thiazol-2-yl]propane-1,2-diol | Ligand Info | |||||
| Structure Description | ROS1 with AstraZeneca ligand 2 | PDB:7Z5X | ||||
| Method | X-ray diffraction | Resolution | 2.04 Å | Mutation | No | [3] |
| PDB Sequence |
LPAFPREKLT
1946 LRLLLGSGAF1956 GEVYEGTAVD1966 ILGVGSGEIK1976 VAVKTLKKGS1986 TDQEKIEFLK 1996 EAHLMSKFNH2006 PNILKQLGVC2016 LLNEPQYIIL2026 ELMEGGDLLT2036 YLRKARMATF 2046 YGPLLTLVDL2056 VDLCVDISKG2066 CVYLERMHFI2076 HRDLAARNCL2086 VSVKDYTSPR 2096 IVKIGDFLPV2125 RWMAPESLMD2135 GIFTTQSDVW2145 SFGILIWEIL2155 TLGHQPYPAH 2165 SNLDVLNYVQ2175 TGGRLEPPRN2185 CPDDLWNLMT2195 QCWAQEPDQR2205 PTFHRIQDQL 2215 QLFRNFFLNS2225
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .AWJ or .AWJ2 or .AWJ3 or :3AWJ;style chemicals stick;color identity;select .A:1951 or .A:1952 or .A:1953 or .A:1954 or .A:1959 or .A:1978 or .A:1980 or .A:2010 or .A:2026 or .A:2027 or .A:2028 or .A:2029 or .A:2030 or .A:2031 or .A:2032 or .A:2033 or .A:2036 or .A:2083 or .A:2084 or .A:2085 or .A:2086 or .A:2101 or .A:2102; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
LEU1951
3.721
GLY1952
3.974
SER1953
4.463
GLY1954
4.556
VAL1959
3.680
ALA1978
3.471
LYS1980
4.220
LEU2010
3.753
LEU2026
3.975
GLU2027
2.867
LEU2028
3.733
MET2029
3.039
|
|||||
| Ligand Name: N-[6-methyl-2-[(2S)-2-[3-(3-methylpyrazin-2-yl)-1,2-oxazol-5-yl]pyrrolidin-1-yl]pyrimidin-4-yl]-1,3-thiazol-2-amine | Ligand Info | |||||
| Structure Description | ROS1 with AstraZeneca ligand 1 | PDB:7Z5W | ||||
| Method | X-ray diffraction | Resolution | 2.25 Å | Mutation | No | [3] |
| PDB Sequence |
LPAFPREKLT
1946 LRLLLGSGAF1956 GEVYEGTAVD1966 ILGVGSGEIK1976 VAVKTLKKGS1986 TDQEKIEFLK 1996 EAHLMSKFNH2006 PNILKQLGVC2016 LLNEPQYIIL2026 ELMEGGDLLT2036 YLRKARMATF 2046 YGPLLTLVDL2056 VDLCVDISKG2066 CVYLERMHFI2076 HRDLAARNCL2086 VSVKDYTSPR 2096 IVKIGDFGLP2124 VRWMAPESLM2134 DGIFTTQSDV2144 WSFGILIWEI2154 LTLGHQPYPA 2164 HSNLDVLNYV2174 QTGGRLEPPR2184 NCPDDLWNLM2194 TQCWAQEPDQ2204 RPTFHRIQDQ 2214 LQLFRNFFLN2224 S
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .IDW or .IDW2 or .IDW3 or :3IDW;style chemicals stick;color identity;select .A:1951 or .A:1952 or .A:1953 or .A:1959 or .A:1978 or .A:2010 or .A:2026 or .A:2027 or .A:2028 or .A:2029 or .A:2030 or .A:2031 or .A:2032 or .A:2033 or .A:2083 or .A:2084 or .A:2085 or .A:2086 or .A:2101 or .A:2102; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
LEU1951
3.540
GLY1952
3.825
SER1953
4.868
VAL1959
3.675
ALA1978
3.213
LEU2010
4.184
LEU2026
3.888
GLU2027
3.229
LEU2028
3.863
MET2029
2.945
|
|||||
| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Acquired resistance to crizotinib from a mutation in CD74-ROS1. N Engl J Med. 2013 Jun 20;368(25):2395-401. | ||||
| REF 2 | PF-06463922 is a potent and selective next-generation ROS1/ALK inhibitor capable of blocking crizotinib-resistant ROS1 mutations. Proc Natl Acad Sci U S A. 2015 Mar 17;112(11):3493-8. | ||||
| REF 3 | Virtual Screening in the Cloud Identifies Potent and Selective ROS1 Kinase Inhibitors. J Chem Inf Model. 2022 Aug 22;62(16):3832-3843. | ||||
If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.