Target Information
| Target General Information | Top | |||||
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| Target ID |
T62073
(Former ID: TTDR00249)
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| Target Name |
Ornithine delta-aminotransferase (OAT)
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| Synonyms |
Ornithine--oxo-acid aminotransferase; Ornithine aminotransferase, mitochondrial
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| Gene Name |
OAT
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| Target Type |
Literature-reported target
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[1] | ||||
| Function |
Catalyzes the transfer of the delta-amino group from L-ornithine.
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| BioChemical Class |
Transaminase
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| UniProt ID | ||||||
| EC Number |
EC 2.6.1.13
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| Sequence |
MFSKLAHLQRFAVLSRGVHSSVASATSVATKKTVQGPPTSDDIFEREYKYGAHNYHPLPV
ALERGKGIYLWDVEGRKYFDFLSSYSAVNQGHCHPKIVNALKSQVDKLTLTSRAFYNNVL GEYEEYITKLFNYHKVLPMNTGVEAGETACKLARKWGYTVKGIQKYKAKIVFAAGNFWGR TLSAISSSTDPTSYDGFGPFMPGFDIIPYNDLPALERALQDPNVAAFMVEPIQGEAGVVV PDPGYLMGVRELCTRHQVLFIADEIQTGLARTGRWLAVDYENVRPDIVLLGKALSGGLYP VSAVLCDDDIMLTIKPGEHGSTYGGNPLGCRVAIAALEVLEEENLAENADKLGIILRNEL MKLPSDVVTAVRGKGLLNAIVIKETKDWDAWKVCLRLRDNGLLAKPTHGDIIRFAPPLVI KEDELRESIEIINKTILSF Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| 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: Pyridoxal phosphate | Ligand Info | |||||
| Structure Description | (1S,3S)-3-amino-4-(perfluoropropan-2-ylidene)cyclopentane-1-carboxylic acid hydrochloride, a potent inhibitor of ornithine aminotransferase | PDB:6OIA | ||||
| Method | X-ray diffraction | Resolution | 1.78 Å | Mutation | No | [3] |
| PDB Sequence |
GPPTSDDIFE
45 REYKYGAHNY55 HPLPVALERG65 KGIYLWDVEG75 RKYFDFLSSY85 SAVNQGHCHP 95 KIVNALKSQV105 DKLTLTSRAF115 YNNVLGEYEE125 YITKLFNYHK135 VLPMNTGVEA 145 GETACKLARK155 WGYTVKGIQK165 YKAKIVFAAG175 NFWGRTLSAI185 SSSTDPTSYD 195 GFGPFMPGFD205 IIPYNDLPAL215 ERALQDPNVA225 AFMVEPIQGE235 AGVVVPDPGY 245 LMGVRELCTR255 HQVLFIADEI265 QTGLARTGRW275 LAVDYENVRP285 DIVLLGKALS 295 GGLYPVSAVL305 CDDDIMLTIK315 PGEHGSTYGG325 NPLGCRVAIA335 ALEVLEEENL 345 AENADKLGII355 LRNELMKLPS365 DVVTAVRGKG375 LLNAIVIKET385 KDWDAWKVCL 395 RLRDNGLLAK405 PTHGDIIRFA415 PPLVIKEDEL425 RESIEIINKT435 ILSF |
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: Canaline | Ligand Info | |||||
| Structure Description | HUMAN ORNITHINE AMINOTRANSFERASE COMPLEXED WITH L-CANALINE | PDB:2CAN | ||||
| Method | X-ray diffraction | Resolution | 2.30 Å | Mutation | No | [4] |
| PDB Sequence |
PTSDDIFERE
47 YKYGAHNYHP57 LPVALERGKG67 IYLWDVEGRK77 YFDFLSSYSA87 VNQGHCHPKI 97 VNALKSQVDK107 LTLTSRAFYN117 NVLGEYEEYI127 TKLFNYHKVL137 PMNTGVEAGE 147 TACKLARKWG157 YTVKGIQKYK167 AKIVFAAGNF177 WGRTLSAISS187 STDPTSYDGF 197 GPFMPGFDII207 PYNDLPALER217 ALQDPNVAAF227 MVEPIQGEAG237 VVVPDPGYLM 247 GVRELCTRHQ257 VLFIADEIQT267 GLARTGRWLA277 VDYENVRPDI287 VLLGKALSGG 297 LYPVSAVLCD307 DDIMLTIKPG317 EHGSTYGGNP327 LGCRVAIAAL337 EVLEEENLAE 347 NADKLGIILR357 NELMKLPSDV367 VTAVRGKGLL377 NAIVIKETKD387 WDAWKVCLRL 397 RDNGLLAKPT407 HGDIIRFAPP417 LVIKEDELRE427 SIEIINKTIL437 SF |
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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 Pathway Affiliation
of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.
Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes
(Pharmacol Rev, 58: 259-279, 2006).
Biological Network Descriptors
of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.
The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information
(Front Pharmacol, 9, 1245, 2018;
Curr Opin Struct Biol. 44:134-142, 2017).
Human Similarity Proteins
Human Tissue Distribution
Human Pathway Affiliation
Biological Network Descriptors
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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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| KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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| Arginine and proline metabolism | hsa00330 | Affiliated Target |
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| Class: Metabolism => Amino acid metabolism | Pathway Hierarchy | ||
| Degree | 6 | Degree centrality | 6.45E-04 | Betweenness centrality | 2.33E-04 |
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| Closeness centrality | 1.71E-01 | Radiality | 1.27E+01 | Clustering coefficient | 3.33E-01 |
| Neighborhood connectivity | 8.83E+00 | Topological coefficient | 2.85E-01 | Eccentricity | 13 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Target Affiliated Biological Pathways | Top | |||||
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| BioCyc | [+] 1 BioCyc Pathways | + | ||||
| 1 | Ornithine de novo biosynthesis | |||||
| KEGG Pathway | [+] 3 KEGG Pathways | + | ||||
| 1 | Arginine and proline metabolism | |||||
| 2 | Metabolic pathways | |||||
| 3 | Biosynthesis of antibiotics | |||||
| Pathwhiz Pathway | [+] 1 Pathwhiz Pathways | + | ||||
| 1 | Arginine and Proline Metabolism | |||||
| Reactome | [+] 1 Reactome Pathways | + | ||||
| 1 | Amino acid synthesis and interconversion (transamination) | |||||
| WikiPathways | [+] 2 WikiPathways | + | ||||
| 1 | Urea cycle and metabolism of amino groups | |||||
| 2 | Metabolism of amino acids and derivatives | |||||
| References | Top | |||||
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| REF 1 | How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6. | |||||
| REF 2 | Ornithine aminotransferase, a potential target for the treatment of hyperammonemias. Curr Drug Targets. 2000 Sep;1(2):119-53. | |||||
| REF 3 | Mechanism of Inactivation of Ornithine Aminotransferase by (1S,3S)-3-Amino-4-(hexafluoropropan-2-ylidenyl)cyclopentane-1-carboxylic Acid. J Am Chem Soc. 2019 Jul 10;141(27):10711-10721. | |||||
| REF 4 | Human ornithine aminotransferase complexed with L-canaline and gabaculine: structural basis for substrate recognition. Structure. 1997 Aug 15;5(8):1067-75. | |||||
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