Binding Site Information of Target
| 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 | |||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| Ligand Name: Xanthosine-5'-monophosphate | Ligand Info | |||||
| Structure Description | Crystal Structure of human ATIC in complex with XMP | PDB:1PKX | ||||
| Method | X-ray diffraction | Resolution | 1.90 Å | Mutation | No | [1] |
| PDB Sequence |
PGQLALFSVS
12 DKTGLVEFAR22 NLTALGLNLV32 ASGGTAKALR42 DAGLAVRDVS52 ELTGFPEMLG 62 GRVKTLHPAV72 HAGILARNIP82 EDNADMARLD92 FNLIRVVACN102 LYPFVKTVAS 112 PGVTVEEAVE122 QIDIGGVTLL132 RAAAKNHARV142 TVVCEPEDYV152 VVSTEMQSSE 162 SKDTSLETRR172 QLALKAFTHT182 AQYDEAISDY192 FRKQYSKGVS202 QMPLRYGMNP 212 HQTPAQLYTL222 QPKLPITVLN232 GAPGFINLCD242 ALNAWQLVKE252 LKEALGIPAA 262 ASFKHVSPAG272 AAVGIPLSED282 EAKVCMVYDL292 YKTLTPISAA302 YARARGADRM 312 SSFGDFVALS322 DVCDVPTAKI332 ISREVSDGII342 APGYEEEALT352 ILSKKKNGNY 362 CVLQMDQSYK372 PDENEVRTLF382 GLHLSQKRNN392 GVVDKSLFSN402 VVTKNKDLPE 412 SALRDLIVAT422 IAVKYTQSNS432 VCYAKNGQVI442 GIGAGQQSRI452 HCTRLAGDKA 462 NYWWLRHHPQ472 VLSMKFKTGV482 AEISNAIDQY494 VTGTIGEDED504 LIKWKALFEE 514 VPELLTEAEK524 KEWVEKLTEV534 SISSDAFFPF544 RDNVDRAKRS554 GVAYIAAPSG 564 SAADKVVIEA574 CDELGIILAH584 TNLRLFHH
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SER10
3.081
VAL11
3.657
SER12
2.959
LYS14
2.887
SER34
2.656
GLY35
3.839
GLY36
3.080
THR37
2.730
ALA38
4.741
GLU59
4.590
GLY63
3.847
ARG64
2.775
VAL65
3.750
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: N-[(S)-(4-{[(2-Amino-4-hydroxyquinazolin-6-YL)(dihydroxy)-lambda~4~-sulfanyl]amino}phenyl)(hydroxy)methyl]-L-glutamic acid | Ligand Info | |||||
| Structure Description | Crystal Structure of Human ATIC in complex with folate-based inhibitor BW1540U88UD | PDB:1P4R | ||||
| Method | X-ray diffraction | Resolution | 2.55 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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| Ligand Name: AICA ribonucleotide | Ligand Info | |||||
| Structure Description | Crystal structure of AICARFT bound to an antifolate | PDB:5UZ0 | ||||
| Method | X-ray diffraction | Resolution | 1.79 Å | Mutation | No | [3] |
| 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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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .AMZ or .AMZ2 or .AMZ3 or :3AMZ;style chemicals stick;color identity;select .A:10 or .A:11 or .A:12 or .A:14 or .A:34 or .A:35 or .A:36 or .A:37 or .A:38 or .A:59 or .A:63 or .A:64 or .A:65 or .A:66 or .A:67 or .A:68 or .A:101 or .A:102 or .A:103 or .A:104 or .A:125 or .A:126 or .A:127 or .A:128 or .A:131 or .A:431 or .A:451 or .A:540 or .A:541 or .A:542 or .A:543 or .A:588 or .A:590; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
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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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: 5-[(5S)-5-ethyl-5-methyl-6-oxo-1,4-dihydropyridin-3-yl]-N-(6-fluoro-1-oxo-2H-isoquinolin-7-yl)thiophene-2-sulfonamide | Ligand Info | |||||
| Structure Description | Crystal structure of AICARFT bound to an antifolate | PDB:5UY8 | ||||
| Method | X-ray diffraction | Resolution | 2.39 Å | Mutation | No | [3] |
| 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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Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .8UM or .8UM2 or .8UM3 or :38UM;style chemicals stick;color identity;select .A:266 or .A:267 or .A:312 or .A:313 or .A:314 or .A:315 or .A:316 or .A:337 or .A:339 or .A:358 or .A:489; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Structural insights into the human and avian IMP cyclohydrolase mechanism via crystal structures with the bound XMP inhibitor. Biochemistry. 2004 Feb 10;43(5):1171-83. | ||||
| REF 2 | 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 3 | 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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