Target Information
| Target General Information | Top | |||||
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| Target ID |
T72881
(Former ID: TTDR00232)
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| Target Name |
Leukotriene C4 synthase (LTC4S)
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| Synonyms |
Leukotriene-C(4)Leukotriene C4 synthase synthase; Leukotriene-C(4) synthase; LTC4 synthase
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| Gene Name |
LTC4S
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| Target Type |
Patented-recorded target
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[1] | ||||
| Function |
Catalyzes the conjugation of leukotriene A4 with reduced glutathione to form leukotriene C4.
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| BioChemical Class |
Carbon-sulfur lyase
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| UniProt ID | ||||||
| EC Number |
EC 4.4.1.20
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| Sequence |
MKDEVALLAAVTLLGVLLQAYFSLQVISARRAFRVSPPLTTGPPEFERVYRAQVNCSEYF
PLFLATLWVAGIFFHEGAAALCGLVYLFARLRYFQGYARSAQLRLAPLYASARALWLLVA LAALGLLAHFLPAALRAALLGRLRTLLPWA Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| HIT2.0 ID | T42P8F | |||||
| 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: Glutathione | Ligand Info | |||||
| Structure Description | Crystal structure analysis of human leukotriene C4 synthase at 1.9 angstrom resolution | PDB:3PCV | ||||
| Method | X-ray diffraction | Resolution | 1.90 Å | Mutation | No | [4] |
| PDB Sequence |
MKDEVALLAA
10 VTLLGVLLQA20 YFSLQVISAR30 RAFRVSPPLT40 TGPPEFERVY50 RAQVNCSEYF 60 PLFLATLWVA70 GIFFHEGAAA80 LCGLVYLFAR90 LRYFQGYARS100 AQLRLAPLYA 110 SARALWLLVA120 LAALGLLAHF130 LPAALRAALL140 GRLRTL
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: Palmitoleic acid | Ligand Info | |||||
| Structure Description | Structure of human Leukotriene C4 synthase mutant R31Q in complex with glutathione | PDB:3LEO | ||||
| Method | X-ray diffraction | Resolution | 2.10 Å | Mutation | Yes | [5] |
| PDB Sequence |
HHHHHHKDEV
5 ALLAAVTLLG15 VLLQAYFSLQ25 VISARQAFRV35 SPPLTTGPPE45 FERVYRAQVN 55 CSEYFPLFLA65 TLWVAGIFFH75 EGAAALCGLV85 YLFARLRYFQ95 GYARSAQLRL 105 APLYASARAL115 WLLVALAALG125 LLAHFLPAAL135 RAALLGRLRT145 |
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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 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 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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| KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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| Arachidonic acid metabolism | hsa00590 | Affiliated Target |
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| Class: Metabolism => Lipid metabolism | Pathway Hierarchy | ||
| Degree | 2 | Degree centrality | 2.15E-04 | Betweenness centrality | 0.00E+00 |
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| Closeness centrality | 1.60E-01 | Radiality | 1.24E+01 | Clustering coefficient | 1.00E+00 |
| Neighborhood connectivity | 4.50E+00 | Topological coefficient | 6.43E-01 | Eccentricity | 14 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Chemical Structure based Activity Landscape of Target | Top |
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| Drug Property Profile of Target | Top | |
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| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| Target Regulators | Top | |||||
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| Target-regulating Transcription Factors | ||||||
| Target-interacting Proteins | ||||||
| References | Top | |||||
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| REF 1 | Leukotriene C4 synthase: a candidate gene for the aspirin-intolerant asthmatic phenotype. Allergy Asthma Proc. 1999 Nov-Dec;20(6):353-60. | |||||
| REF 2 | COMPOUNDS AND USES. US20160326143. | |||||
| REF 3 | Compounds and uses. US9657001. | |||||
| REF 4 | The catalytic architecture of leukotriene C4 synthase with two arginine residues. J Biol Chem. 2011 May 6;286(18):16392-401. | |||||
| REF 5 | Arginine 104 is a key catalytic residue in leukotriene C4 synthase. J Biol Chem. 2010 Dec 24;285(52):40771-6. | |||||
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