Binding Site Information of Target
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T98022 | Target Info | |||
| Target Name | Carboxypeptidase B2 (CPB2) | ||||
| Synonyms | Thrombin-activable fibrinolysis inhibitor; TAFI; Plasma carboxypeptidase B; Carboxypeptidase U; CPU; CPB2 | ||||
| Target Type | Clinical trial Target | ||||
| Gene Name | CPB2 | ||||
| Biochemical Class | Peptidase | ||||
| UniProt ID | |||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| Ligand Name: Arginine | Ligand Info | |||||
| Structure Description | Crystal structure of a T325I/T329I/H333Y/H335Q mutant of Thrombin-Activatable Fibrinolysis Inhibitor (TAFI-IIYQ) | PDB:3D68 | ||||
| Method | X-ray diffraction | Resolution | 2.80 Å | Mutation | Yes | [1] |
| PDB Sequence |
AQSGQVLAAL
10 PRTSRQVQVL20 QNLTTTYEIV30 LWQPVTADLI40 VKKKQVHFFV50 NASDVDNVKA 60 HLNVSGIPCS70 VLLADVEDLI80 QQQISNDTVS90 PRASASYYEQ100 YHSLNEIYSW 110 IEFITERHPD120 MLTKIHIGSS130 FEKYPLYVLK140 VSGKEQTAKN150 AIWIDCGIHA 160 REWISPAFCL170 WFIGHITQFY180 GIIGQYTNLL190 RLVDFYVMPV200 VNVDGYDYSW 210 KKNRMWRKNR220 SFYANNHCIG230 TDLNRNFASK240 HWCEEGASSS250 SCSETYCGLY 260 PESEPEVKAV270 ASFLRRNINQ280 IKAYISMHSY290 SQHIVFPYSY300 TRSKSKDHEE 310 LSLVASEAVR320 AIEKISKNIR330 YTYGQGSETL340 YLAPGGGDDW350 IYDLGIKYSF 360 TIELRDTGTY370 GFLLPERYIK380 PTCREAFAAV390 SKIAWHVIRN400 V |
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| Ligand Name: (2-Guanidinoethylmercapto)succinic acid | Ligand Info | |||||
| Structure Description | Crystal structure of Thrombin-Activatable Fibrinolysis Inhibitor (TAFI) in complex with 2-guanidino-ethyl-mercaptosuccinic acid (GEMSA) | PDB:3D67 | ||||
| Method | X-ray diffraction | Resolution | 3.40 Å | Mutation | No | [1] |
| PDB Sequence |
AQSGQVLAAL
10 PRTSRQVQVL20 QNLTTTYEIV30 LWQPVTADLI40 VKKKQVHFFV50 NASDVDNVKA 60 HLNVSGIPCS70 VLLADVEDLI80 QQQISNDTVS90 PRASASYYEQ100 YHSLNEIYSW 110 IEFITERHPD120 MLTKIHIGSS130 FEKYPLYVLK140 VSGKEQTAKN150 AIWIDCGIHA 160 REWISPAFCL170 WFIGHITQFY180 GIIGQYTNLL190 RLVDFYVMPV200 VNVDGYDYSW 210 KKNRMWRKNR220 SFYANNHCIG230 TDLNRNFASK240 HWCEEGASSS250 SCSETYCGLY 260 PESEPEVKAV270 ASFLRRNINQ280 IKAYISMHSY290 SQHIVFPYSY300 TRSKSKDHEE 310 LSLVASEAVR320 AIEKTSKNTR330 YTHGHGSETL340 YLAPGGGDDW350 IYDLGIKYSF 360 TIELRDTGTY370 GFLLPERYIK380 PTCREAFAAV390 SKIAWHVIRN400 V |
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| Ligand Name: (5r)-5-(3-Aminopropyl)-1-Propyl-4,5,6,7-Tetrahydro-1h-Benzimidazole-5-Carboxylic Acid | Ligand Info | |||||
| Structure Description | pro-carboxypeptidase U In Complex With 5-(3-aminopropyl)-1-propyl-6,7-dihydro-4H-benzimidazole-5-carboxylic acid | PDB:4P10 | ||||
| Method | X-ray diffraction | Resolution | 2.00 Å | Mutation | Yes | [2] |
| PDB Sequence |
SGQVLAALPR
34 TSRQVQVLQN44 LTTTYEIVLW54 QPVTADLIVK64 KKQVHFFVNA74 SDVDNVKAHL 84 NVSGIPCSVL94 LADVEDLIQQ104 QISNDTVSPR114 ASASYYEQYH124 SLNEIYSWIE 134 FITERHPDML144 TKIHIGSSFE154 KYPLYVLKVS164 GKEQAAKNAI174 WIDCGIHARE 184 WISPAFCLWF194 IGHITQFYGI204 IGQYTNLLRL214 VDFYVMPVVN224 VDGYDYSWKK 234 NRMWRKNRSF244 YANNHCIGTD254 LNRNFASKHW264 CEEGASSSSC274 SETYCGLYPE 284 SEPEVKAVAS294 FLRRNINQIK304 AYISMHSYSQ314 HIVFPYSYTR324 SKSKDHEELS 334 LVASEAVRAI344 EKTSKNTRYT354 YGQGSETLYL364 APGGGDDWIY374 DLGIKYSFTI 384 ELRDTGTYGF394 LLPERYIKPT404 CREAFAAVSK414 IAWHVIRNVL424 EP |
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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 .2B8 or .2B82 or .2B83 or :32B8;style chemicals stick;color identity;select .A:54 or .A:55 or .A:181 or .A:184 or .A:239 or .A:256 or .A:257 or .A:310 or .A:311 or .A:312 or .A:313 or .A:317 or .A:321 or .A:362 or .A:365 or .A:368 or .A:369 or .A:370 or .A:383 or .A:385 or .A:394; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
TRP54
3.739
GLN55
3.966
HIS181
3.164
GLU184
3.118
ARG239
4.046
ASN256
2.896
ARG257
2.905
HIS310
3.323
SER311
2.978
TYR312
3.699
SER313
4.707
|
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| Ligand Name: (1R,3S)-3-(4-ammoniobutyl)-1-benzyl-1,4-azaphosphinan-1-ium-3-carboxylate 4,4-dioxide | Ligand Info | |||||
| Structure Description | Inhibitor Complex with Thrombin Activatable Fibrinolysis inhibitor (TAFIa) | PDB:7NEE | ||||
| Method | X-ray diffraction | Resolution | 2.55 Å | Mutation | No | [3] |
| PDB Sequence |
QSGQVLAALP
33 RTSRQVQVLQ43 NLTTTYEIVL53 WQPVTADLIV63 KKKQVHFFVN73 ASDVDNVKAH 83 LNVSGIPCSV93 LLADVEDLIQ103 QQISNDTVSP113 RASASYYEQY123 HSLNEIYSWI 133 EFITERHPDM143 LTKIHIGSSF153 EKYPLYVLKV163 SGKEQAAKNA173 IWIDCGIHAR 183 EWISPAFCLW193 FIGHITQFYG203 IIGQYTNLLR213 LVDFYVMPVV223 NVDGYDYSWK 233 KNRMWRKNRS243 FYANNHCIGT253 DLNRNFASKH263 WCEEGASSSS273 CSETYCGLYP 283 ESEPEVKAVA293 SFLRRNINQI303 KAYISMHSYS313 QHIVFPYSYT323 RSKCKDHEEL 333 SLVASEAVRA343 IEKISKNIRY353 TYGQGSETLY363 LAPGGGDDWI373 YDLGIKYSFT 383 IELRDTGTYG393 FLLPERYIKP403 TCREAFAAVS413 KIAWHVIRNV423 |
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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 .U9B or .U9B2 or .U9B3 or :3U9B;style chemicals stick;color identity;select .A:57 or .A:181 or .A:184 or .A:239 or .A:256 or .A:257 or .A:310 or .A:311 or .A:312 or .A:313 or .A:317 or .A:321 or .A:358 or .A:359 or .A:361 or .A:363 or .A:364 or .A:365 or .A:368 or .A:369 or .A:370 or .A:371 or .A:383 or .A:385 or .A:394; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
VAL57
3.970
HIS181
2.185
GLU184
3.336
ARG239
2.376
ASN256
2.388
ARG257
2.376
HIS310
2.482
SER311
3.469
TYR312
3.571
SER313
3.558
VAL317
2.929
SER321
1.626
GLY358
2.733
|
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| Ligand Name: (1R,3S)-3-(4-ammoniobutyl)-1-(4-fluoro-2-(1-methyl-1H-imidazol-5-yl)benzyl)-1,4-azaphosphinan-1-ium-3-carboxylate 4,4-dioxide | Ligand Info | |||||
| Structure Description | Inhibitor Complex with Thrombin Activatable Fibrinolysis Inhibitor (TAFIa) | PDB:7NEU | ||||
| Method | X-ray diffraction | Resolution | 2.80 Å | Mutation | No | [3] |
| PDB Sequence |
QSGQVLAALP
11 RTSRQVQVLQ21 NLTTTYEIVL31 WQPVTADLIV41 KKKQVHFFVN51 ASDVDNVKAH 61 LNVSGIPCSV71 LLADVEDLIQ81 QQISNDTVSP91 RASASYYEQY101 HSLNEIYSWI 111 EFITERHPDM121 LTKIHIGSSF131 EKYPLYVLKV141 SGQTAKNAIW153 IDCGIHAREW 163 ISPAFCLWFI173 GHITQFYGII183 GQYTNLLRLV193 DFYVMPVVNV203 DGYDYSWKKN 213 RMWRKNRSFY223 ANNHCIGTDL233 NRNFASKHWC243 EEGASSSSCS253 ETYCGLYPES 263 EPEVKAVASF273 LRRNINQIKA283 YISMHSYSQH293 IVFPYSYTRS303 KCKDHEELSL 313 VASEAVRAIE323 KISKNIRYTY333 GQGSETLYLA343 PGGGDDWIYD353 LGIKYSFTIE 363 LRDTGTYGFL373 LPERYIKPTC383 REAFAAVSKI393 AWHVIRNV
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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 .U9K or .U9K2 or .U9K3 or :3U9K;style chemicals stick;color identity;select .A:34 or .A:35 or .A:39 or .A:159 or .A:162 or .A:217 or .A:232 or .A:234 or .A:235 or .A:255 or .A:286 or .A:288 or .A:289 or .A:290 or .A:291 or .A:293 or .A:295 or .A:298 or .A:299 or .A:336 or .A:337 or .A:339 or .A:341 or .A:342 or .A:343 or .A:346 or .A:347 or .A:348 or .A:349 or .A:361 or .A:363 or .A:372; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
|
PRO34
3.414
VAL35
3.503
LEU39
3.168
HIS159
2.203
GLU162
3.566
ARG217
2.031
ASP232
4.931
ASN234
2.165
ARG235
2.228
THR255
4.818
SER286
4.450
HIS288
2.516
SER289
3.136
TYR290
3.383
SER291
3.601
HIS293
4.152
|
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Crystal structures of TAFI elucidate the inactivation mechanism of activated TAFI: a novel mechanism for enzyme autoregulation. Blood. 2008 Oct 1;112(7):2803-9. | ||||
| REF 2 | Design and synthesis of conformationally restricted inhibitors of active thrombin activatable fibrinolysis inhibitor (TAFIa). Bioorg Med Chem. 2014 Apr 1;22(7):2261-8. | ||||
| REF 3 | Phosphinanes and Azaphosphinanes as Potent and Selective Inhibitors of Activated Thrombin-Activatable Fibrinolysis Inhibitor (TAFIa). J Med Chem. 2021 Apr 8;64(7):3897-3910. | ||||
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