Binding Site Information of Target
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T14558 | Target Info | |||
| Target Name | Tryptase alpha/beta-1 (Tryptase) | ||||
| Synonyms | Tryptase-1; Tryptase alpha-1; Tryptase I; TPSB1; TPS2; TPS1 | ||||
| Target Type | Successful Target | ||||
| Gene Name | TPSAB1 | ||||
| Biochemical Class | Peptidase | ||||
| UniProt ID | |||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| Ligand Name: (3'-{4-[3-(aminomethyl)phenyl]piperidine-1-carbonyl}[1,1'-biphenyl]-3-yl){4-[3-(aminomethyl)phenyl]piperidin-1-yl}[3,4-di(hydroxy-kappaO)phenyl]methanonato(2-)hydroxyborate(1-) | Ligand Info | |||||
| Structure Description | Human beta-tryptase co-crystal structure with 5-{4-[3-(aminomethyl)phenyl]piperidine-1-carbonyl}-2-(3'-{4-[3-(aminomethyl)phenyl]piperidine-1-carbonyl}-[1,1'-biphenyl]-3-yl)-2-hydroxy-2H-1,3,2-benzodioxaborol-2-uide | PDB:6P0P | ||||
| Method | X-ray diffraction | Resolution | 2.55 Å | Mutation | No | [1] |
| PDB Sequence |
IVGGQEAPRS
40 KWPWQVSLRV50 HGPYWMHFCG60 GSLIHPQWVL70 TAAHCVGPDV80 KDLAALRVQL 90 REQHLYYQDQ100 LLPVSRIIVH110 PQFYTAQIGA120 DIALLELEEP130 VKVSSHVHTV 140 TLPPASETFP150 PGMPCWVTGW160 GDVDNDERLP170 PPFPLKQVKV180 PIMENHICDA 190 KYHLGAYTGD200 DVRIVRDDML210 CAGNTRRDSC220 QGDSGGPLVC230 KVNGTWLQAG 240 VVSWGEGCAQ250 PNRPGIYTRV260 TYYLDWIHHY270 VPK
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| Ligand Name: (R,R)-2,3-butanediol | Ligand Info | |||||
| Structure Description | Crystal Structure of the Recombinant Human Alpha I Tryptase Mutant K192Q/D216G in Complex with Leupeptin | PDB:2F9N | ||||
| Method | X-ray diffraction | Resolution | 1.60 Å | Mutation | Yes | [2] |
| PDB Sequence |
IVGGQEAPRS
25 KWPWQVSLRV35 RDRYWMHFCG43 GSLIHPQWVL53 TAAHCVGPDV60C KDLATLRVQL 68 REQHLYYQDQ81 LLPVSRIIVH91 PQFYIIQTGA101 DIALLELEEP111 VNISSRVHTV 121 MLPPASETFP131 PGMPCWVTGW141 GDVDNDEPLP152 PPFPLKQVKV160 PIMENHICDA 170 KYHLGAYTGD173G DVRIIRDDML181 CAGNSQRDSC191 QGDSGGPLVC201 KVNGTWLQAG 211 VVSWGEGCAQ221A PNRPGIYTRV231 TYYLDWIHHY241 VPK
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: amino{[(4S)-4-amino-5,5-dihydroxypentyl]amino}methaniminium | Ligand Info | |||||
| Structure Description | Crystal Structure of the Recombinant Human Alpha I Tryptase Mutant K192Q/D216G in Complex with Leupeptin | PDB:2F9N | ||||
| Method | X-ray diffraction | Resolution | 1.60 Å | Mutation | Yes | [2] |
| PDB Sequence |
IVGGQEAPRS
25 KWPWQVSLRV35 RDRYWMHFCG43 GSLIHPQWVL53 TAAHCVGPDV60C KDLATLRVQL 68 REQHLYYQDQ81 LLPVSRIIVH91 PQFYIIQTGA101 DIALLELEEP111 VNISSRVHTV 121 MLPPASETFP131 PGMPCWVTGW141 GDVDNDEPLP152 PPFPLKQVKV160 PIMENHICDA 170 KYHLGAYTGD173G DVRIIRDDML181 CAGNSQRDSC191 QGDSGGPLVC201 KVNGTWLQAG 211 VVSWGEGCAQ221A PNRPGIYTRV231 TYYLDWIHHY241 VPK
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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 .AR7 or .AR72 or .AR73 or :3AR7;style chemicals stick;color identity;select .A:42 or .A:57 or .A:189 or .A:190 or .A:191 or .A:192 or .A:193 or .A:194 or .A:195 or .A:213 or .A:214 or .A:215 or .A:216 or .A:217 or .A:219 or .A:220 or .A:221 or .A:224 or .A:226 or .A:227 or .A:228; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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CYS42
4.919
HIS57
2.810
ASP189
2.864
SER190
3.017
CYS191
3.535
GLN192
3.510
GLY193
4.320
ASP194
4.752
SER195
1.414
VAL213
3.802
SER214
2.958
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: (5~{s})-5-[[3-(Aminomethyl)phenoxy]methyl]-3-[3-[2-(2-Chloranylpyridin-3-Yl)ethynyl]phenyl]-1,3-Oxazolidin-2-One | Ligand Info | |||||
| Structure Description | TRYPTASE B2 IN COMPLEX WITH 5-(3-Aminomethyl-phenoxymethyl)-3-[3-(2-chloro-pyridin-3-ylethynyl)-phenyl]-oxazolidin-2-one; compound with trifluoro-acetic acid | PDB:5F03 | ||||
| Method | X-ray diffraction | Resolution | 1.94 Å | Mutation | No | [3] |
| PDB Sequence |
IVGGQEAPRS
25 KWPWQVSLRV35 HGPYWMHFCG43 GSLIHPQWVL53 TAAHCVGPDV60C KDLAALRVQL 68 REQHLYYQDQ81 LLPVSRIIVH91 PQFYTAQIGA101 DIALLELEEP111 VKVSSHVHTV 121 TLPPASETFP131 PGMPCWVTGW141 GDVDNDERLP152 PPFPLKQVKV160 PIMENHICDA 170 KYHLGAYTGD173G DVRIVRDDML181 CAGNTRRDSC191 QGDSGGPLVC201 KVNGTWLQAG 211 VVSWGEGCAQ221A PNRPGIYTRV231 TYYLDWIHHY241 VP
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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 .5TA or .5TA2 or .5TA3 or :35TA;style chemicals stick;color identity;select .A:98 or .A:172 or .A:173C or .A:173E or .A:175 or .A:189 or .A:190 or .A:191 or .A:192 or .A:195 or .A:213 or .A:214 or .A:215 or .A:216 or .A:217 or .A:219 or .A:220 or .A:221 or .A:224 or .A:226 or .A:227; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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GLN98
2.799
TYR172
3.270
ALA173C
4.158
THR173E
4.644
ILE175
3.672
ASP189
2.785
SER190
2.859
CYS191
3.489
GLN192
3.445
SER195
3.363
VAL213
3.573
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| Ligand Name: (2r,4s)-N,N'-Bis[3-({4-[3-(Aminomethyl)phenyl]piperidin-1-Yl}carbonyl)phenyl]-4-Hydroxy-2-(2-Hydroxypropan-2-Yl)-5,5-Dimethyl-1,3-Dioxolane-2,4-Dicarboxamide | Ligand Info | |||||
| Structure Description | Human beta-tryptase co-crystal structure with (2R,4S)-N,N'-bis[3-({4-[3-(aminomethyl)phenyl]piperidin-1-yl}carbonyl)phenyl]-4-hydroxy-2-(2-hydroxypropan-2-yl)-5,5-dimethyl-1,3-dioxolane-2,4-dicarboxamide | PDB:4MPV | ||||
| Method | X-ray diffraction | Resolution | 2.31 Å | Mutation | No | [4] |
| PDB Sequence |
IVGGQEAPRS
40 KWPWQVSLRV50 HGPYWMHFCG60 GSLIHPQWVL70 TAAHCVGPDV80 KDLAALRVQL 90 REQHLYYQDQ100 LLPVSRIIVH110 PQFYTAQIGA120 DIALLELEEP130 VKVSSHVHTV 140 TLPPASETFP150 PGMPCWVTGW160 GDVDNDERLP170 PPFPLKQVKV180 PIMENHICDA 190 KYHLGAYTGD200 DVRIVRDDML210 CAGNTRRDSC220 QGDSGGPLVC230 KVNGTWLQAG 240 VVSWGEGCAQ250 PNRPGIYTRV260 TYYLDWIHHY270 VPK
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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 .2A4 or .2A42 or .2A43 or :32A4;style chemicals stick;color identity;select .A:114 or .A:115 or .A:117 or .A:218 or .A:219 or .A:220 or .A:221 or .A:224 or .A:242 or .A:243 or .A:244 or .A:245 or .A:246 or .A:247 or .A:248 or .A:255 or .A:256; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: L-Alpha-Glutamyl-N-{(1s)-4-{[amino(Iminio)methyl]amino}-1-[(1s)-2-Chloro-1-Hydroxyethyl]butyl}glycinamide | Ligand Info | |||||
| Structure Description | Human beta-1 tryptase mutant Ile99Cys | PDB:5WI6 | ||||
| Method | X-ray diffraction | Resolution | 2.72 Å | Mutation | Yes | [5] |
| PDB Sequence |
IVGGQEAPRS
25 KWPWQVSLRV35 HGPYWMHFCG43 GSLIHPQWVL53 TAAHCVGPDV60C KDLAALRVQL 68 REQHLYYQDQ81 LLPVSRIIVH91 PQFYTAQCGA101 DIALLELEEP111 VNVSSHVHTV 121 TLPPASETFP131 PGMPCWVTGW141 GDVDNDERLP152 PPFPLKQVKV160 PIMENHICDA 170 KYHLGAYTGD173G DVRIVRDDML181 CAGNTRRDSC191 QGDSGGPLVC201 KVNGTWLQAG 211 VVSWGEGCAQ221A PNRPGIYTRV231 TYYLDWIHHY241 VPK
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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 .0GJ or .0GJ2 or .0GJ3 or :30GJ;style chemicals stick;color identity;select .A:41 or .A:42 or .A:57 or .A:58 or .A:97 or .A:98 or .A:189 or .A:190 or .A:191 or .A:192 or .A:193 or .A:194 or .A:195 or .A:213 or .A:214 or .A:215 or .A:216 or .A:217 or .A:219 or .A:220 or .A:226 or .A:227 or .A:228; color #f3c393; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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PHE41
4.849
CYS42
4.778
HIS57
1.448
CYS58
4.705
ALA97
4.253
GLN98
3.084
ASP189
3.144
SER190
2.925
CYS191
3.557
GLN192
3.266
GLY193
3.050
ASP194
3.998
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: 1-[1'-(3-Phenylacryloyl)spiro[1-benzofuran-3,4'-piperidin]-5-yl]methanamine | Ligand Info | |||||
| Structure Description | Potent, Nonpeptide Inhibitors of Human Mast Cell Tryptase | PDB:2ZEC | ||||
| Method | X-ray diffraction | Resolution | 2.06 Å | Mutation | No | [6] |
| PDB Sequence |
IVGGQEAPRS
25 KWPWQVSLRV35 HGPYWMHFCG45 GSLIHPQWVL55 TAAHCVGPDV65 KDLAALRVQL 75 REQHLYYQDQ85 LLPVSRIIVH95 PQFYTAQIGA105 DIALLELEEP115 VKVSSHVHTV 125 TLPPASETFP135 PGMPCWVTGW145 GDVDNDERLP155 PPFPLKQVKV165 PIMENHICDA 175 KYHLGAYTGD185 DVRIVRDDML195 CAGNTRRDSC205 QGDSGGPLVC215 KVNGTWLQAG 225 VVSWGEGCAQ235 PNRPGIYTRV245 TYYLDWIHHY255 VPK
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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 .11N or .11N2 or .11N3 or :311N;style chemicals stick;color identity;select .A:102 or .A:203 or .A:204 or .A:205 or .A:206 or .A:207 or .A:209 or .A:227 or .A:228 or .A:229 or .A:230 or .A:231 or .A:232 or .A:233 or .A:234 or .A:240 or .A:241; color #00ffc7; zoom selection;set surface opacity 0.5;set surface Van der Waals surface;set mode all
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| Ligand Name: 1-(1'-{[3-(Methylsulfanyl)-2-benzothiophen-1-yl]carbonyl}spiro[1-benzofuran-3,4'-piperidin]-5-yl)methanamine | Ligand Info | |||||
| Structure Description | Potent, Nonpeptide Inhibitors of Human Mast Cell Tryptase | PDB:2ZEB | ||||
| Method | X-ray diffraction | Resolution | 2.50 Å | Mutation | No | [6] |
| PDB Sequence |
IVGGQEAPRS
10 KWPWQVSLRV20 HGPYWMHFCG30 GSLIHPQWVL40 TAAHCVGPDV50 KDLAALRVQL 60 REQHLYYQDQ70 LLPVSRIIVH80 PQFYTAQIGA90 DIALLELEEP100 VKVSSHVHTV 110 TLPPASETFP120 PGMPCWVTGW130 GDVDNDERLP140 PPFPLKQVKV150 PIMENHICDA 160 KYHLGAYTGD170 DVRIVRDDML180 CAGNTRRDSC190 QGDSGGPLVC200 KVNGTWLQAG 210 VVSWGEGCAQ220 PNRPGIYTRV230 TYYLDWIHHY240 VPK
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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 .11M or .11M2 or .11M3 or :311M;style chemicals stick;color identity;select .A:87 or .A:188 or .A:189 or .A:190 or .A:191 or .A:192 or .A:194 or .A:212 or .A:213 or .A:214 or .A:215 or .A:216 or .A:217 or .A:218 or .A:219 or .A:225 or .A:226; 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 | Novel, Self-Assembling Dimeric Inhibitors of Human Beta Tryptase. J Med Chem. 2020 Mar 26;63(6):3004-3027. | ||||
| REF 2 | X-ray structures of free and leupeptin-complexed human alphaI-tryptase mutants: indication for an alpha-->beta-tryptase transition. J Mol Biol. 2006 Mar 17;357(1):195-209. | ||||
| REF 3 | A Real-World Perspective on Molecular Design. J Med Chem. 2016 May 12;59(9):4087-102. | ||||
| REF 4 | Target-Directed Self-Assembly of Homodimeric Drugs Against Beta-Tryptase. ACS Med Chem Lett. 2018 Jul 5;9(8):827-831. | ||||
| REF 5 | Dual functionality of Beta-tryptase protomers as both proteases and cofactors in the active tetramer. J Biol Chem. 2018 Jun 22;293(25):9614-9628. | ||||
| REF 6 | Potent, nonpeptide inhibitors of human mast cell tryptase. Synthesis and biological evaluation of novel spirocyclic piperidine amide derivatives. Bioorg Med Chem Lett. 2008 Mar 15;18(6):2114-21. | ||||
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