Target Information
| Target General Information | Top | |||||
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| Target ID |
T86829
(Former ID: TTDR00037)
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| Target Name |
Fungal Scytalone dehydratase (Fung SDH1)
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| Synonyms |
SDH1
Click to Show/Hide
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| Gene Name |
Fung SDH1
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| Target Type |
Literature-reported target
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[1] | ||||
| Function |
Catalyzes two steps in melanin biosynthesis. From scytalone they are two dehydration steps and one reduction step to yield melanin.
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| BioChemical Class |
Alpha-carbonic anhydrase
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| UniProt ID | ||||||
| EC Number |
EC 4.2.1.94
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| Sequence |
MGSQVQKSDEITFSDYLGLMTCVYEWADSYDSKDWDRLRKVIAPTLRIDYRSFLDKLWEA
MPAEEFVGMVSSKQVLGDPTLRTQHFIGGTRWEKVSEDEVIGYHQLRVPHQRYKDTTMKE VTMKGHAHSANLHWYKKIDGVWKFAGLKPDIRWGEFDFDRIFEDGRETFGDK Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| Drug Binding Sites of Target | Top | |||||
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| Ligand Name: 4-(3,3-Diphenylpropylamino)cinnoline-3-carbonitrile | Ligand Info | |||||
| Structure Description | SCYTALONE DEHYDRATASE AND CYANOCINNOLINE INHIBITOR | PDB:3STD | ||||
| Method | X-ray diffraction | Resolution | 1.65 Å | Mutation | No | [4] |
| PDB Sequence |
GEITFSDYLG
18 LMTCVYEWAD28 SYDSKDWDRL38 RKVIAPTLRI48 DYRSFLDKLW58 EAMPAEEFVG 68 MVSSKQVLGD78 PTLRTQHFIG88 GTRWEKVSED98 EVIGYHQLRV108 PHQRYKDTTM 118 KEVTMKGHAH128 SANLHWYKKI138 DGVWKFAGLK148 PDIRWGEFDF158 DRIFEDGRET 168 FG
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TRP26
4.041
TYR30
2.819
TYR50
2.921
PHE53
3.364
LEU54
3.752
PHE66
4.477
MET69
4.135
VAL70
4.109
VAL75
3.851
LEU76
4.475
HIS85
3.930
LEU106
3.863
VAL108
3.477
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| Ligand Name: (1R,3R)-N-[(1R)-1-(4-bromophenyl)ethyl]-2,2-dichloro-3-methyl-1-[(S)-methylsulfinyl]cyclopropane-1-carboxamide | Ligand Info | |||||
| Structure Description | SCYTALONE DEHYDRATASE PLUS INHIBITOR 3 | PDB:6STD | ||||
| Method | X-ray diffraction | Resolution | 1.80 Å | Mutation | No | [5] |
| PDB Sequence |
GEITFSDYLG
18 LMTCVYEWAD28 SYDSKDWDRL38 RKVIAPTLRI48 DYRSFLDKLW58 EAMPAEEFVG 68 MVSSKQVLGD78 PTLRTQHFIG88 GTRWEKVSED98 EVIGYHQLRV108 PHQRYKDTTM 118 KEVTMKGHAH128 SANLHWYKKI138 DGVWKFAGLK148 PDIRWGEFDF158 DRIFEDGRET 168 FGDK
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TRP26
3.693
TYR30
3.844
TYR50
2.834
PHE53
3.294
LEU54
3.864
MET69
4.100
VAL70
4.561
VAL75
3.629
LEU76
3.563
HIS85
3.796
LEU106
3.702
VAL108
3.670
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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 Similarity Proteins
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There is no similarity protein (E value < 0.005) for this target
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| 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-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 1 | Enzymatic characterization of scytalone dehydratase Val75Met variant found in melanin biosynthesis dehydratase inhibitor (MBI-D) resistant strains of the rice blast fungus. Biosci Biotechnol Biochem.2004 Mar;68(3):615-21. | |||||
| REF 2 | A diazine heterocycle replaces a six-membered hydrogen-bonded array in the active site of scytalone dehydratase, Bioorg. Med. Chem. Lett. 3(8):1605-1608 (1993). | |||||
| REF 3 | Binding dynamics of two water molecules constrained within the scytalone dehydratase binding pocket. Bioorg Med Chem Lett. 2000 Jan 3;10(1):23-6. | |||||
| REF 4 | Structure-based design of potent inhibitors of scytalone dehydratase: displacement of a water molecule from the active site. Biochemistry. 1998 Dec 22;37(51):17735-44. | |||||
| REF 5 | High-resolution structures of scytalone dehydratase-inhibitor complexes crystallized at physiological pH. Proteins. 1999 Jun 1;35(4):425-39. | |||||
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