Target Binding Site Detail
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T03691 | Target Info | |||
| Target Name | Leukotriene A-4 hydrolase (LTA4H) | ||||
| Synonyms | Leukotriene A4 hydrolase; Leukotriene A(4)Leukotriene A-4 hydrolase hydrolase; Leukotriene A(4) hydrolase; LTA4; LTA-H; LTA-4hydrolase; LTA-4 hydrolase | ||||
| Target Type | Successful Target | ||||
| Gene Name | LTA4H | ||||
| Biochemical Class | Ether bond hydrolase | ||||
| UniProt ID | |||||
| Ligand General Information | Top | ||||
|---|---|---|---|---|---|
| Ligand Name | Bestatin | Ligand Info | |||
| Canonical SMILES | CC(C)CC(C(=O)O)NC(=O)C(C(CC1=CC=CC=C1)N)O | ||||
| InChI | 1S/C16H24N2O4/c1-10(2)8-13(16(21)22)18-15(20)14(19)12(17)9-11-6-4-3-5-7-11/h3-7,10,12-14,19H,8-9,17H2,1-2H3,(H,18,20)(H,21,22)/t12-,13+,14+/m1/s1 | ||||
| InChIKey | VGGGPCQERPFHOB-RDBSUJKOSA-N | ||||
| PubChem Compound ID | 72172 | ||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| PDB ID: 3FUH Leukotriene A4 hydrolase in complex with fragment 5-hydroxyindole and bestatin | ||||||
| Method | X-ray diffraction | Resolution | 1.80 Å | Mutation | No | [1] |
| PDB Sequence |
VDTCSLASPA
13 SVCRTKHLHL23 RCSVDFTRRT33 LTGTAALTVQ43 SQEDNLRSLV53 LDTKDLTIEK 63 VVINGQEVKY73 ALGERQSYKG83 SPMEISLPIA93 LSKNQEIVIE103 ISFETSPKSS 113 ALQWLTPEQT123 SGKEHPYLFS133 QCQAIHCRAI143 LPCQDTPSVK153 LTYTAEVSVP 163 KELVALMSAI173 RDGETPDPED183 PSRKIYKFIQ193 KVPIPCYLIA203 LVVGALESRQ 213 IGPRTLVWSE223 KEQVEKSAYE233 FSETESMLKI243 AEDLGGPYVW253 GQYDLLVLPP 263 SFPYGGMENP273 CLTFVTPTLL283 AGDKSLSNVI293 AHEISHSWTG303 NLVTNKTWDH 313 FWLNEGHTVY323 LERHICGRLF333 GEKFRHFNAL343 GGWGELQNSV353 KTFGETHPFT 363 KLVVDLTDID373 PDVAYSSVPY383 EKGFALLFYL393 EQLLGGPEIF403 LGFLKAYVEK 413 FSYKSITTDD423 WKDFLYSYFK433 DKVDVLNQVD443 WNAWLYSPGL453 PPIKPNYDMT 463 LTNACIALSQ473 RWITAKEDDL483 NSFNATDLKD493 LSSHQLNEFL503 AQTLQRAPLP 513 LGHIKRMQEV523 YNFNAINNSE533 IRFRWLRLCI543 QSKWEDAIPL553 ALKMATEQGR 563 MKFTRPLFKD573 LAAFDKSHDQ583 AVRTYQEHKA593 SMHPVTAMLV603 GKDLKVD |
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|
|
GLN134
3.663
GLN136
2.780
ALA137
4.077
TYR267
3.300
GLY268
2.750
GLY269
3.239
MET270
3.368
GLU271
2.609
ASN291
3.873
VAL292
4.003
|
|||||
| PDB ID: 1HS6 STRUCTURE OF LEUKOTRIENE A4 HYDROLASE COMPLEXED WITH BESTATIN. | ||||||
| Method | X-ray diffraction | Resolution | 1.95 Å | Mutation | No | [2] |
| PDB Sequence |
PEIVDTCSLA
10 SPASVCRTKH20 LHLRCSVDFT30 RRTLTGTAAL40 TVQSQEDNLR50 SLVLDTKDLT 60 IEKVVINGQE70 VKYALGERQS80 YKGSPMEISL90 PIALSKNQEI100 VIEISFETSP 110 KSSALQWLTP120 EQTSGKEHPY130 LFSQCQAIHC140 RAILPCQDTP150 SVKLTYTAEV 160 SVPKELVALM170 SAIRDGETPD180 PEDPSRKIYK190 FIQKVPIPCY200 LIALVVGALE 210 SRQIGPRTLV220 WSEKEQVEKS230 AYEFSETESM240 LKIAEDLGGP250 YVWGQYDLLV 260 LPPSFPYGGM270 ENPCLTFVTP280 TLLAGDKSLS290 NVIAHEISHS300 WTGNLVTNKT 310 WDHFWLNEGH320 TVYLERHICG330 RLFGEKFRHF340 NALGGWGELQ350 NSVKTFGETH 360 PFTKLVVDLT370 DIDPDVAYSS380 VPYEKGFALL390 FYLEQLLGGP400 EIFLGFLKAY 410 VEKFSYKSIT420 TDDWKDFLYS430 YFKDKVDVLN440 QVDWNAWLYS450 PGLPPIKPNY 460 DMTLTNACIA470 LSQRWITAKE480 DDLNSFNATD490 LKDLSSHQLN500 EFLAQTLQRA 510 PLPLGHIKRM520 QEVYNFNAIN530 NSEIRFRWLR540 LCIQSKWEDA550 IPLALKMATE 560 QGRMKFTRPL570 FKDLAAFDKS580 HDQAVRTYQE590 HKASMHPVTA600 MLVGKDLKVD 610
|
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|
|
GLN134
3.690
GLN136
2.788
ALA137
3.984
TYR267
3.253
GLY268
2.620
GLY269
3.246
MET270
3.622
GLU271
2.542
ASN291
4.055
VAL292
3.918
|
|||||
| PDB ID: 3FTX Leukotriene A4 hydrolase in complex with dihydroresveratrol and bestatin | ||||||
| Method | X-ray diffraction | Resolution | 1.96 Å | Mutation | No | [1] |
| PDB Sequence |
VDTCSLASPA
13 SVCRTKHLHL23 RCSVDFTRRT33 LTGTAALTVQ43 SQEDNLRSLV53 LDTKDLTIEK 63 VVINGQEVKY73 ALGERQSYKG83 SPMEISLPIA93 LSKNQEIVIE103 ISFETSPKSS 113 ALQWLTPEQT123 SGKEHPYLFS133 QCQAIHCRAI143 LPCQDTPSVK153 LTYTAEVSVP 163 KELVALMSAI173 RDGETPDPED183 PSRKIYKFIQ193 KVPIPCYLIA203 LVVGALESRQ 213 IGPRTLVWSE223 KEQVEKSAYE233 FSETESMLKI243 AEDLGGPYVW253 GQYDLLVLPP 263 SFPYGGMENP273 CLTFVTPTLL283 AGDKSLSNVI293 AHEISHSWTG303 NLVTNKTWDH 313 FWLNEGHTVY323 LERHICGRLF333 GEKFRHFNAL343 GGWGELQNSV353 KTFGETHPFT 363 KLVVDLTDID373 PDVAYSSVPY383 EKGFALLFYL393 EQLLGGPEIF403 LGFLKAYVEK 413 FSYKSITTDD423 WKDFLYSYFK433 DKVDVLNQVD443 WNAWLYSPGL453 PPIKPNYDMT 463 LTNACIALSQ473 RWITAKEDDL483 NSFNATDLKD493 LSSHQLNEFL503 AQTLQRAPLP 513 LGHIKRMQEV523 YNFNAINNSE533 IRFRWLRLCI543 QSKWEDAIPL553 ALKMATEQGR 563 MKFTRPLFKD573 LAAFDKSHDQ583 AVRTYQEHKA593 SMHPVTAMLV603 GKDLKVD |
|||||
|
|
GLN134
3.701
GLN136
2.753
ALA137
4.150
TYR267
3.275
GLY268
2.671
GLY269
3.114
MET270
3.345
GLU271
2.489
ASN291
3.799
VAL292
4.024
HIS295
3.216
|
|||||
| PDB ID: 3FUE Leukotriene A4 hydrolase in complex with fragment 5-chloroindole and bestatin | ||||||
| Method | X-ray diffraction | Resolution | 2.38 Å | Mutation | No | [1] |
| PDB Sequence |
VDTCSLASPA
13 SVCRTKHLHL23 RCSVDFTRRT33 LTGTAALTVQ43 SQEDNLRSLV53 LDTKDLTIEK 63 VVINGQEVKY73 ALGERQSYKG83 SPMEISLPIA93 LSKNQEIVIE103 ISFETSPKSS 113 ALQWLTPEQT123 SGKEHPYLFS133 QCQAIHCRAI143 LPCQDTPSVK153 LTYTAEVSVP 163 KELVALMSAI173 RDGETPDPED183 PSRKIYKFIQ193 KVPIPCYLIA203 LVVGALESRQ 213 IGPRTLVWSE223 KEQVEKSAYE233 FSETESMLKI243 AEDLGGPYVW253 GQYDLLVLPP 263 SFPYGGMENP273 CLTFVTPTLL283 AGDKSLSNVI293 AHEISHSWTG303 NLVTNKTWDH 313 FWLNEGHTVY323 LERHICGRLF333 GEKFRHFNAL343 GGWGELQNSV353 KTFGETHPFT 363 KLVVDLTDID373 PDVAYSSVPY383 EKGFALLFYL393 EQLLGGPEIF403 LGFLKAYVEK 413 FSYKSITTDD423 WKDFLYSYFK433 DKVDVLNQVD443 WNAWLYSPGL453 PPIKPNYDMT 463 LTNACIALSQ473 RWITAKEDDL483 NSFNATDLKD493 LSSHQLNEFL503 AQTLQRAPLP 513 LGHIKRMQEV523 YNFNAINNSE533 IRFRWLRLCI543 QSKWEDAIPL553 ALKMATEQGR 563 MKFTRPLFKD573 LAAFDKSHDQ583 AVRTYQEHKA593 SMHPVTAMLV603 GKDLKVD |
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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 .BES or .BES2 or .BES3 or :3BES;style chemicals stick;color identity;select .A:134 or .A:136 or .A:137 or .A:267 or .A:268 or .A:269 or .A:270 or .A:271 or .A:291 or .A:292 or .A:295 or .A:296 or .A:299 or .A:314 or .A:318 or .A:325 or .A:378 or .A:383 or .A:563 or .A:565; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
GLN134
3.439
GLN136
2.755
ALA137
4.025
TYR267
3.169
GLY268
2.662
GLY269
3.012
MET270
3.555
GLU271
2.561
ASN291
3.811
VAL292
4.102
|
|||||
| PDB ID: 3FUF Leukotriene A4 hydrolase in complex with fragment 5-fluoroindole and bestatin | ||||||
| Method | X-ray diffraction | Resolution | 2.60 Å | Mutation | No | [1] |
| PDB Sequence |
VDTCSLASPA
13 SVCRTKHLHL23 RCSVDFTRRT33 LTGTAALTVQ43 SQEDNLRSLV53 LDTKDLTIEK 63 VVINGQEVKY73 ALGERQSYKG83 SPMEISLPIA93 LSKNQEIVIE103 ISFETSPKSS 113 ALQWLTPEQT123 SGKEHPYLFS133 QCQAIHCRAI143 LPCQDTPSVK153 LTYTAEVSVP 163 KELVALMSAI173 RDGETPDPED183 PSRKIYKFIQ193 KVPIPCYLIA203 LVVGALESRQ 213 IGPRTLVWSE223 KEQVEKSAYE233 FSETESMLKI243 AEDLGGPYVW253 GQYDLLVLPP 263 SFPYGGMENP273 CLTFVTPTLL283 AGDKSLSNVI293 AHEISHSWTG303 NLVTNKTWDH 313 FWLNEGHTVY323 LERHICGRLF333 GEKFRHFNAL343 GGWGELQNSV353 KTFGETHPFT 363 KLVVDLTDID373 PDVAYSSVPY383 EKGFALLFYL393 EQLLGGPEIF403 LGFLKAYVEK 413 FSYKSITTDD423 WKDFLYSYFK433 DKVDVLNQVD443 WNAWLYSPGL453 PPIKPNYDMT 463 LTNACIALSQ473 RWITAKEDDL483 NSFNATDLKD493 LSSHQLNEFL503 AQTLQRAPLP 513 LGHIKRMQEV523 YNFNAINNSE533 IRFRWLRLCI543 QSKWEDAIPL553 ALKMATEQGR 563 MKFTRPLFKD573 LAAFDKSHDQ583 AVRTYQEHKA593 SMHPVTAMLV603 GKDLKVD |
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .BES or .BES2 or .BES3 or :3BES;style chemicals stick;color identity;select .A:134 or .A:136 or .A:137 or .A:267 or .A:268 or .A:269 or .A:270 or .A:271 or .A:291 or .A:292 or .A:295 or .A:296 or .A:299 or .A:314 or .A:318 or .A:325 or .A:378 or .A:383 or .A:563 or .A:565; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
GLN134
3.657
GLN136
2.780
ALA137
4.064
TYR267
3.123
GLY268
2.651
GLY269
3.050
MET270
3.732
GLU271
2.555
ASN291
3.939
VAL292
4.144
|
|||||
| PDB ID: 1GW6 STRUCTURE OF LEUKOTRIENE A4 HYDROLASE D375N MUTANT | ||||||
| Method | X-ray diffraction | Resolution | 2.20 Å | Mutation | Yes | [3] |
| PDB Sequence |
PEIVDTCSLA
10 SPASVCRTKH20 LHLRCSVDFT30 RRTLTGTAAL40 TVQSQEDNLR50 SLVLDTKDLT 60 IEKVVINGQE70 VKYALGERQS80 YKGSPMEISL90 PIALSKNQEI100 VIEISFETSP 110 KSSALQWLTP120 EQTSGKEHPY130 LFSQCQAIHC140 RAILPCQDTP150 SVKLTYTAEV 160 SVPKELVALM170 SAIRDGETPD180 PEDPSRKIYK190 FIQKVPIPCY200 LIALVVGALE 210 SRQIGPRTLV220 WSEKEQVEKS230 AYEFSETESM240 LKIAEDLGGP250 YVWGQYDLLV 260 LPPSFPYGGM270 ENPCLTFVTP280 TLLAGDKSLS290 NVIAHEISHS300 WTGNLVTNKT 310 WDHFWLNEGH320 TVYLERHICG330 RLFGEKFRHF340 NALGGWGELQ350 NSVKTFGETH 360 PFTKLVVDLT370 DIDPNVAYSS380 VPYEKGFALL390 FYLEQLLGGP400 EIFLGFLKAY 410 VEKFSYKSIT420 TDDWKDFLYS430 YFKDKVDVLN440 QVDWNAWLYS450 PGLPPIKPNY 460 DMTLTNACIA470 LSQRWITAKE480 DDLNSFNATD490 LKDLSSHQLN500 EFLAQTLQRA 510 PLPLGHIKRM520 QEVYNFNAIN530 NSEIRFRWLR540 LCIQSKWEDA550 IPLALKMATE 560 QGRMKFTRPL570 FKDLAAFDKS580 HDQAVRTYQE590 HKASMHPVTA600 MLVGKDLKVD 610
|
|||||
|
Click to Show 3D Structure of This Binding Site
set background white;style ions nothing; color 8e8e8e;style chemicals nothing; select .BES or .BES2 or .BES3 or :3BES;style chemicals stick;color identity;select .A:134 or .A:136 or .A:137 or .A:267 or .A:268 or .A:269 or .A:270 or .A:271 or .A:291 or .A:292 or .A:295 or .A:296 or .A:299 or .A:314 or .A:318 or .A:325 or .A:378 or .A:383 or .A:563 or .A:565; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
GLN134
3.525
GLN136
2.720
ALA137
3.854
TYR267
3.227
GLY268
2.536
GLY269
3.129
MET270
3.497
GLU271
2.585
ASN291
3.882
VAL292
3.951
|
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Discovery of leukotriene A4 hydrolase inhibitors using metabolomics biased fragment crystallography. J Med Chem. 2009 Aug 13;52(15):4694-715. | ||||
| REF 2 | Crystal structure of human leukotriene A(4) hydrolase, a bifunctional enzyme in inflammation. Nat Struct Biol. 2001 Feb;8(2):131-5. | ||||
| REF 3 | Leukotriene A4 hydrolase: selective abrogation of leukotriene B4 formation by mutation of aspartic acid 375. Proc Natl Acad Sci U S A. 2002 Apr 2;99(7):4215-20. | ||||
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