Target Information
| Target General Information | Top | |||||
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| Target ID |
T34239
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| Target Name |
Protoporphyrinogen oxidase (PPOX)
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| Synonyms |
PPO
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| Gene Name |
PPOX
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| Target Type |
Successful target
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[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Epidermal dysplasias [ICD-11: EK90] | |||||
| Function |
Catalyzes the 6-electron oxidation of protoporphyrinogen-IX to form protoporphyrin-IX.
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| UniProt ID | ||||||
| EC Number |
EC 1.3.3.4
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| Sequence |
MGRTVVVLGGGISGLAASYHLSRAPCPPKVVLVESSERLGGWIRSVRGPNGAIFELGPRG
IRPAGALGARTLLLVSELGLDSEVLPVRGDHPAAQNRFLYVGGALHALPTGLRGLLRPSP PFSKPLFWAGLRELTKPRGKEPDETVHSFAQRRLGPEVASLAMDSLCRGVFAGNSRELSI RSCFPSLFQAEQTHRSILLGLLLGAGRTPQPDSALIRQALAERWSQWSLRGGLEMLPQAL ETHLTSRGVSVLRGQPVCGLSLQAEGRWKVSLRDSSLEADHVISAIPASVLSELLPAEAA PLARALSAITAVSVAVVNLQYQGAHLPVQGFGHLVPSSEDPGVLGIVYDSVAFPEQDGSP PGLRVTVMLGGSWLQTLEASGCVLSQELFQQRAQEAAATQLGLKEMPSHCLVHLHKNCIP QYTLGHWQKLESARQFLTAHRLPLTLAGASYEGVAVNDCIESGRQAAVSVLGTEPNS Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| Drugs and Modes of Action | Top | |||||
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| Approved Drug(s) | [+] 1 Approved Drugs | + | ||||
| 1 | Aminolevulinic Acid Hydrochloride | Drug Info | Approved | Actinic keratosis | [2] | |
| Mode of Action | [+] 1 Modes of Action | + | ||||
| Modulator | [+] 1 Modulator drugs | + | ||||
| 1 | Aminolevulinic Acid Hydrochloride | Drug Info | [1] | |||
| 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: Flavin-Adenine Dinucleotide | Ligand Info | |||||
| Structure Description | Structure of human protoporphyrinogen IX oxidase | PDB:3NKS | ||||
| Method | X-ray diffraction | Resolution | 1.90 Å | Mutation | No | [3] |
| PDB Sequence |
GRTVVVLGGG
11 ISGLAASYHL21 SRAPCPPKVV31 LVESSERLGG41 WIRSVRGPNG51 AIFELGPRGI 61 RPAGALGART71 LLLVSELGLD81 SEVLPVRGDH91 PAAQNRFLYV101 GGALHALPTG 111 LRGPSPPFSK124 PLFWAGLREL134 TKPRGKEPDE144 TVHSFAQRRL154 GPEVASLAMD 164 SLCRGVFAGN174 SRELSIRSCF184 PSLFQAEQTH194 RSILLGLLLG204 QPDSALIRQA 219 LAERWSQWSL229 RGGLEMLPQA239 LETHLTSRGV249 SVLRGQPVCG259 LSLQAEGRWK 269 VSLRDSSLEA279 DHVISAIPAS289 VLSELLPAEA299 APLARALSAI309 TAVSVAVVNL 319 QYQGAHLPVQ329 GFGHLVPSSE339 DPGVLGIVYD349 SVAFPEQDGS359 PPGLRVTVML 369 GGSWLQTLEA379 SGCVLSQELF389 QQRAQEAAAT399 QLGLKEMPSH409 CLVHLHKNCI 419 PQYTLGHWQK429 LESARQFLTA439 HRLPLTLAGA449 SYEGVAVNDC459 IESGRQAAVS 469 VLGTE
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LEU8
4.689
GLY9
3.357
GLY10
4.122
GLY11
3.486
ILE12
3.555
SER13
3.039
GLY14
4.454
VAL33
3.075
GLU34
2.666
SER35
3.000
SER36
4.260
GLY40
4.246
GLY41
3.220
TRP42
2.966
ILE43
4.230
LEU56
3.637
GLY57
3.462
PRO58
3.252
ARG59
3.637
GLY60
3.678
GLN255
4.191
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: Acifluorfen | Ligand Info | |||||
| Structure Description | Structure of human protoporphyrinogen IX oxidase | PDB:3NKS | ||||
| Method | X-ray diffraction | Resolution | 1.90 Å | Mutation | No | [3] |
| PDB Sequence |
GRTVVVLGGG
11 ISGLAASYHL21 SRAPCPPKVV31 LVESSERLGG41 WIRSVRGPNG51 AIFELGPRGI 61 RPAGALGART71 LLLVSELGLD81 SEVLPVRGDH91 PAAQNRFLYV101 GGALHALPTG 111 LRGPSPPFSK124 PLFWAGLREL134 TKPRGKEPDE144 TVHSFAQRRL154 GPEVASLAMD 164 SLCRGVFAGN174 SRELSIRSCF184 PSLFQAEQTH194 RSILLGLLLG204 QPDSALIRQA 219 LAERWSQWSL229 RGGLEMLPQA239 LETHLTSRGV249 SVLRGQPVCG259 LSLQAEGRWK 269 VSLRDSSLEA279 DHVISAIPAS289 VLSELLPAEA299 APLARALSAI309 TAVSVAVVNL 319 QYQGAHLPVQ329 GFGHLVPSSE339 DPGVLGIVYD349 SVAFPEQDGS359 PPGLRVTVML 369 GGSWLQTLEA379 SGCVLSQELF389 QQRAQEAAAT399 QLGLKEMPSH409 CLVHLHKNCI 419 PQYTLGHWQK429 LESARQFLTA439 HRLPLTLAGA449 SYEGVAVNDC459 IESGRQAAVS 469 VLGTE
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| 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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| Porphyrin metabolism | hsa00860 | Affiliated Target |
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| Class: Metabolism => Metabolism of cofactors and vitamins | Pathway Hierarchy | ||
| Degree | 3 | Degree centrality | 3.22E-04 | Betweenness centrality | 0.00E+00 |
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| Closeness centrality | 1.55E-01 | Radiality | 1.22E+01 | Clustering coefficient | 1.00E+00 |
| Neighborhood connectivity | 7.33E+00 | Topological coefficient | 5.24E-01 | Eccentricity | 12 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Chemical Structure based Activity Landscape of Target | Top |
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| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| References | Top | |||||
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| REF 1 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. | |||||
| REF 2 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015 | |||||
| REF 3 | Structural insight into human variegate porphyria disease. FASEB J. 2011 Feb;25(2):653-64. | |||||
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