Target Binding Site Detail
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T04741 | Target Info | |||
| Target Name | Phosphoribosylaminoimidazolecarboxamide formyltransferase (ATIC) | ||||
| Synonyms | PURH; OK/SW-cl.86; Bifunctional purine biosynthesis protein PURH | ||||
| Target Type | Literature-reported Target | ||||
| Gene Name | ATIC | ||||
| Biochemical Class | Methyltransferase | ||||
| UniProt ID | |||||
| Ligand General Information | Top | ||||
|---|---|---|---|---|---|
| Ligand Name | AICA ribonucleotide | Ligand Info | |||
| Canonical SMILES | C1=NC(=C(N1C2C(C(C(O2)COP(=O)(O)O)O)O)N)C(=O)N | ||||
| InChI | 1S/C9H15N4O8P/c10-7-4(8(11)16)12-2-13(7)9-6(15)5(14)3(21-9)1-20-22(17,18)19/h2-3,5-6,9,14-15H,1,10H2,(H2,11,16)(H2,17,18,19)/t3-,5-,6-,9-/m1/s1 | ||||
| InChIKey | NOTGFIUVDGNKRI-UUOKFMHZSA-N | ||||
| PubChem Compound ID | 65110 | ||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| PDB ID: 1P4R Crystal Structure of Human ATIC in complex with folate-based inhibitor BW1540U88UD | ||||||
| Method | X-ray diffraction | Resolution | 2.55 Å | Mutation | No | [1] |
| PDB Sequence |
GQLALFSVSD
13 KTGLVEFARN23 LTALGLNLVA33 SGGTAKALRD43 AGLAVRDVSE53 LTGFPEMLGG 63 RVKTLHPAVH73 AGILARNIPE83 DNADMARLDF93 NLIRVVACNL103 YPFVKTVASP 113 GVTVEEAVEQ123 IDIGGVTLLR133 AAAKNHARVT143 VVCEPEDYVV153 VSTEMQSSES 163 KDTSLETRRQ173 LALKAFTHTA183 QYDEAISDYF193 RKQYSKGVSQ203 MPLRYGMNPH 213 QTPAQLYTLQ223 PKLPITVLNG233 APGFINLCDA243 LNAWQLVKEL253 KEALGIPAAA 263 SFKHVSPAGA273 AVGIPLSEDE283 AKVCMVYDLY293 KTLTPISAAY303 ARARGADRMS 313 SFGDFVALSD323 VCDVPTAKII333 SREVSDGIIA343 PGYEEEALTI353 LSKKKNGNYC 363 VLQMDQSYKP373 DENEVRTLFG383 LHLSQKRNNG393 VVDKSLFSNV403 VTKNKDLPES 413 ALRDLIVATI423 AVKYTQSNSV433 CYAKNGQVIG443 IGAGQQSRIH453 CTRLAGDKAN 463 YWWLRHHPQV473 LSMKFKTGVK483 RAEISNAIDQ493 YVTGTIGEDE503 DLIKWKALFE 513 EVPELLTEAE523 KKEWVEKLTE533 VSISSDAFFP543 FRDNVDRAKR553 SGVAYIAAPS 563 GSAADKVVIE573 ACDELGIILA583 HTNLRLFHH
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| PDB ID: 5UZ0 Crystal structure of AICARFT bound to an antifolate | ||||||
| Method | X-ray diffraction | Resolution | 1.79 Å | Mutation | No | [2] |
| PDB Sequence |
GQLALFSVSD
13 KTGLVEFARN23 LTALGLNLVA33 SGGTAKALRD43 AGLAVRDVSE53 LTGFPEMLGG 63 RVKTLHPAVH73 AGILARNIPE83 DNADMARLDF93 NLIRVVACNL103 YPFVKTVASP 113 GVTVEEAVEQ123 IDIGGVTLLR133 AAAKNHARVT143 VVCEPEDYVV153 VSTEMQSSES 163 KDTSLETRRQ173 LALKAFTHTA183 QYDEAISDYF193 RKQYSKGVSQ203 MPLRYGMNPH 213 QTPAQLYTLQ223 PKLPITVLNG233 APGFINLCDA243 LNAWQLVKEL253 KEALGIPAAA 263 SFKHVSPAGA273 AVGIPLSEDE283 AKVCMVYDLY293 KTLTPISAAY303 ARARGADRMS 313 SFGDFVALSD323 VCDVPTAKII333 SREVSDGIIA343 PGYEEEALTI353 LSKKKNGNYC 363 VLQMDQSYKP373 DENEVRTLFG383 LHLSQKRNNG393 VVDKSLFSNV403 VTKNKDLPES 413 ALRDLIVATI423 AVKYTQSNSV433 CYAKNGQVIG443 IGAGQQSRIH453 CTRLAGDKAN 463 YWWLRHHPQV473 LSMKFKTGVK483 RAEISNAIDQ493 YVTGTIGEDE503 DLIKWKALFE 513 EVPELLTEAE523 KKEWVEKLTE533 VSISSDAFFP543 FRDNVDRAKR553 SGVAYIAAPS 563 GSAADKVVIE573 ACDELGIILA583 HTNLRLFHH
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SER10
3.145
VAL11
3.586
SER12
3.450
LYS14
2.762
SER34
2.636
GLY35
3.939
GLY36
2.902
THR37
2.772
ALA38
4.975
GLU59
4.616
GLY63
3.793
ARG64
2.779
VAL65
3.816
LYS66
2.812
THR67
2.789
LEU68
3.819
CYS101
3.330
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| PDB ID: 5UY8 Crystal structure of AICARFT bound to an antifolate | ||||||
| Method | X-ray diffraction | Resolution | 2.39 Å | Mutation | No | [2] |
| PDB Sequence |
GQLALFSVSD
13 KTGLVEFARN23 LTALGLNLVA33 SGGTAKALRD43 AGLAVRDVSE53 LTGFPEMLGG 63 RVKTLHPAVH73 AGILARNIPE83 DNADMARLDF93 NLIRVVACNL103 YPFVKTVASP 113 GVTVEEAVEQ123 IDIGGVTLLR133 AAAKNHARVT143 VVCEPEDYVV153 VSTEMQSSES 163 KDTSLETRRQ173 LALKAFTHTA183 QYDEAISDYF193 RKQYSKGVSQ203 MPLRYGMNPH 213 QTPAQLYTLQ223 PKLPITVLNG233 APGFINLCDA243 LNAWQLVKEL253 KEALGIPAAA 263 SFKHVSPAGA273 AVGIPLSEDE283 AKVCMVYDLY293 KTLTPISAAY303 ARARGADRMS 313 SFGDFVALSD323 VCDVPTAKII333 SREVSDGIIA343 PGYEEEALTI353 LSKKKNGNYC 363 VLQMDQSYKP373 DENEVRTLFG383 LHLSQKRNNG393 VVDKSLFSNV403 VTKNKDLPES 413 ALRDLIVATI423 AVKYTQSNSV433 CYAKNGQVIG443 IGAGQQSRIH453 CTRLAGDKAN 463 YWWLRHHPQV473 LSMKFKTGVK483 RAEISNAIDQ493 YVTGTIGEDE503 DLIKWKALFE 513 EVPELLTEAE523 KKEWVEKLTE533 VSISSDAFFP543 FRDNVDRAKR553 SGVAYIAAPS 563 GSAADKVVIE573 ACDELGIILA583 HTNLRLFHH
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SER10
3.163
VAL11
3.729
SER12
3.235
LYS14
2.766
SER34
2.624
GLY35
3.766
GLY36
3.035
THR37
2.870
ALA38
4.805
GLU59
4.565
GLY63
3.898
ARG64
2.724
VAL65
3.765
LYS66
2.787
THR67
2.697
LEU68
3.505
CYS101
3.547
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Crystal structures of human bifunctional enzyme aminoimidazole-4-carboxamide ribonucleotide transformylase/IMP cyclohydrolase in complex with potent sulfonyl-containing antifolates. J Biol Chem. 2004 Apr 23;279(17):18034-45. | ||||
| REF 2 | Discovery of N-(6-Fluoro-1-oxo-1,2-dihydroisoquinolin-7-yl)-5-[(3R)-3-hydroxypyrrolidin-1-yl]thiophene-2-sulfonamide (LSN 3213128), a Potent and Selective Nonclassical Antifolate Aminoimidazole-4-carboxamide Ribonucleotide Formyltransferase (AICARFT) Inhibitor Effective at Tumor Suppression in a Cancer Xenograft Model. J Med Chem. 2017 Dec 14;60(23):9599-9616. | ||||
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