Target Information
| Target General Information | Top | |||||
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| Target ID |
T46318
(Former ID: TTDI03014)
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| Target Name |
Acyloxyacyl hydrolase (neutrophil)
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| Synonyms |
Acyloxyacyl hydrolase
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| Gene Name |
AOAH
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| Target Type |
Literature-reported target
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[1] | ||||
| Function |
Removes the secondary (acyloxyacyl-linked) fatty acyl chains from the lipid A region of bacterial lipopolysaccharides. By breaking down LPS, terminates the host response to bacterial infection and prevents prolonged and damaging inflammatory responses (By similarity). In peritoneal macrophages, seems to be important for recovery from a state of immune tolerance following infection by Gram-negative bacteria (By similarity).
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| UniProt ID | ||||||
| EC Number |
EC 3.1.1.77
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| Sequence |
MQSPWKILTVAPLFLLLSLQSSASPANDDQSRPSLSNGHTCVGCVLVVSVIEQLAQVHNS
TVQASMERLCSYLPEKLFLKTTCYLVIDKFGSDIIKLLSADMNADVVCHTLEFCKQNTGQ PLCHLYPLPKETWKFTLQKARQIVKKSPILKYSRSGSDICSLPVLAKICQKIKLAMEQSV PFKDVDSDKYSVFPTLRGYHWRGRDCNDSDESVYPGRRPNNWDVHQDSNCNGIWGVDPKD GVPYEKKFCEGSQPRGIILLGDSAGAHFHISPEWITASQMSLNSFINLPTALTNELDWPQ LSGATGFLDSTVGIKEKSIYLRLWKRNHCNHRDYQNISRNGASSRNLKKFIESLSRNKVL DYPAIVIYAMIGNDVCSGKSDPVPAMTTPEKLYSNVMQTLKHLNSHLPNGSHVILYGLPD GTFLWDNLHNRYHPLGQLNKDMTYAQLYSFLNCLQVSPCHGWMSSNKTLRTLTSERAEQL SNTLKKIAASEKFTNFNLFYMDFAFHEIIQEWQKRGGQPWQLIEPVDGFHPNEVALLLLA DHFWKKVQLQWPQILGKENPFNPQIKQVFGDQGGH Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| Cell-based Target Expression Variations | Top | |||||
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| Cell-based Target Expression Variations | ||||||
| Drug Binding Sites of Target | Top | |||||
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| Ligand Name: Lauric acid | Ligand Info | |||||
| Structure Description | Human acyloxyacyl hydrolase (AOAH), proteolytically processed, S263A mutant, with LPS | PDB:5W7C | ||||
| Method | X-ray diffraction | Resolution | 2.23 Å | Mutation | Yes | [2] |
| PDB Sequence |
GSDICSLPVL
165 AKICQKIKLA175 MEQSVPFKDV185 DSDKYSVFPT195 LRGYHWRGRD205 CNDSDESVYP 215 GRRPNNWDVH225 QDSNCNGIWG235 VDPKDGVPYE245 KKFCEGSQPR255 GIILLGDAAG 265 AHFHISPEWI275 TASQMSLNSF285 INLPTALTNE295 LDWPQLSGAT305 GFLDSTVGIK 315 EKSIYLRLWK325 RNHCNHRDYQ335 NISRNGASSR345 NLKKFIESLS355 RNKVLDYPAI 365 VIYAMIGNDV375 CSGKSDPVPA385 MTTPEKLYSN395 VMQTLKHLNS405 HLPNGSHVIL 415 YGLPDGTFLW425 DNLHNRYHPL435 GQLNKDMTYA445 QLYSFLNCLQ455 VSPCHGWMSS 465 NKTLRTLTSE475 RAEQLSNTLK485 KIAASEKFTN495 FNLFYMDFAF505 HEIIQEWQKR 515 GGQPWQLIEP525 VDGFHPNEVA535 LLLLADHFWK545 KVQLQWPQIL555 GKENPFNPQI 565 KQVFGDQGGH575
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ASP262
2.975
ALA263
2.888
ALA264
2.293
GLY265
4.628
PHE268
4.798
ASN340
2.687
GLY341
3.613
ILE371
2.367
GLY372
2.693
ASN373
2.327
CYS376
3.220
PRO419
2.435
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: Myristic acid | Ligand Info | |||||
| Structure Description | Human acyloxyacyl hydrolase (AOAH), proteolytically processed | PDB:5W78 | ||||
| Method | X-ray diffraction | Resolution | 2.27 Å | Mutation | No | [2] |
| PDB Sequence |
> Chain A
LSNGHTCVGC 44 VLVVSVIEQL54 AQVHNSTVQA64 SMERLCSYLP74 EKLFLKTTCY84 LVIDKFGSDI 94 IKLLSADMNA104 DVVCHTLEFC114 KQNTGQPLCH124 LYPLPKETWK134 FTLQKARQIV 144 KKSPILKY> Chain B DICSLPVLAK 167 ICQKIKLAME177 QSVFPTLRGY199 HWRGRDCNDS209 DESVYPGRRP219 NNWDVHQDSN 229 CNGIWGVDPK239 DGVPYEKKFC249 EGSQPRGIIL259 LGDSAGAHFH269 ISPEWITASQ 279 MSLNSFINLP289 TALTNELDWP299 QLSGATGFLD309 STVGIKEKSI319 YLRLWKRNHC 329 NHRDYQNISR339 NGASSRNLKK349 FIESLSRNKV359 LDYPAIVIYA369 MIGNDVCSGK 379 SDPVPAMTTP389 EKLYSNVMQT399 LKHLNSHLPN409 GSHVILYGLP419 DGTFLWDNLH 429 NRYHPLGQLN439 KDMTYAQLYS449 FLNCLQVSPC459 HGWMSSNKTL469 RTLTSERAEQ 479 LSNTLKKIAA489 SEKFTNFNLF499 YMDFAFHEII509 QEWQKRGGQP519 WQLIEPVDGF 529 HPNEVALLLL539 ADHFWKKVQL549 QWPQILGKEN559 PFNPQIKQVF569 GDQGGH |
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GLY38[A]
4.989
HIS39[A]
2.915
THR40[A]
4.400
VAL42[A]
2.188
GLY43[A]
1.873
CYS44[A]
2.832
LEU46[A]
2.909
VAL47[A]
2.122
VAL48[A]
3.218
ILE51[A]
2.392
MET66[A]
2.498
GLU67[A]
4.868
LEU69[A]
2.122
CYS70[A]
3.068
LEU73[A]
2.798
LEU79[A]
2.727
THR82[A]
2.812
CYS83[A]
2.641
TYR84[A]
4.773
VAL86[A]
2.300
ILE87[A]
2.371
PHE90[A]
2.896
ILE94[A]
2.590
LEU111[A]
3.911
PHE113[A]
2.531
ILE159[B]
2.473
CYS160[B]
4.247
LEU162[B]
2.553
VAL164[B]
4.080
LEU165[B]
2.493
ILE168[B]
2.912
CYS169[B]
3.890
ILE172[B]
2.653
LEU288[B]
3.685
LEU292[B]
2.550
VAL456[B]
4.458
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| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Tissue Distribution
of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.
The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects
(Nat Rev Drug Discov, 20: 64-81, 2021).
Human Similarity Proteins
Human Tissue Distribution
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There is no similarity protein (E value < 0.005) for this target
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Note:
If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.
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| References | Top | |||||
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| REF 1 | A high-throughput, multiplexed assay for superfamily-wide profiling of enzyme activity. Nat Chem Biol. 2014 Aug;10(8):656-63. | |||||
| REF 2 | Crystal structure of the mammalian lipopolysaccharide detoxifier. Proc Natl Acad Sci U S A. 2018 Jan 30;115(5):E896-E905. | |||||
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