Target Information
| Target General Information | Top | |||||
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| Target ID |
T44614
(Former ID: TTDR00606)
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| Target Name |
Plasmodium Cysteine protease falcipain-2 (Malaria CPF2)
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| Synonyms |
Falcipain 2; Cysteine proteinase falcipain 2a
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| Gene Name |
Malaria CPF2
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| Target Type |
Literature-reported target
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[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Malaria [ICD-11: 1F40-1F45] | |||||
| Function |
A papain family cysteine protease and important hemoglobinase of erythrocytic Plasmodium falciparum parasites.
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| BioChemical Class |
Protease
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| UniProt ID | ||||||
| EC Number |
EC 3.4.22.-
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| Sequence |
MDYNMDYAPHEVISQQGERFVDKYVDRKILKNKKSLLVIISLSVLSVVGFVLFYFTPNSR
KSDLFKNSSVENNNDDYIINSLLKSPNGKKFIVSKIDEALSFYDSKKNDINKYNEGNNNN NADFKGLSLFKENTPSNNFIHNKDYFINFFDNKFLMNNAEHINQFYMFIKTNNKQYNSPN EMKERFQVFLQNAHKVNMHNNNKNSLYKKELNRFADLTYHEFKNKYLSLRSSKPLKNSKY LLDQMNYEEVIKKYRGEENFDHAAYDWRLHSGVTPVKDQKNCGSCWAFSSIGSVESQYAI RKNKLITLSEQELVDCSFKNYGCNGGLINNAFEDMIELGGICPDGDYPYVSDAPNLCNID RCTEKYGIKNYLSVPDNKLKEALRFLGPISISVAVSDDFAFYKEGIFDGECGDQLNHAVM LVGFGMKEIVNPLTKKGEKHYYYIIKNSWGQQWGERGFINIETDESGLMRKCGLGTDAFI PLIE Click to Show/Hide
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| Drugs and Modes of Action | Top | |||||
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| Discontinued Drug(s) | [+] 1 Discontinued Drugs | + | ||||
| 1 | Pepstatin | Drug Info | Terminated | Malaria | [2] | |
| Mode of Action | [+] 2 Modes of Action | + | ||||
| Inhibitor | [+] 3 Inhibitor drugs | + | ||||
| 1 | Pepstatin | Drug Info | [1] | |||
| 2 | FITC-LMNNAEHINQFYMFI | Drug Info | [3] | |||
| 3 | Leupeptin | Drug Info | [1] | |||
| Binder | [+] 1 Binder drugs | + | ||||
| 1 | Vinylsulphones | Drug Info | [4] | |||
| Drug Binding Sites of Target | Top | |||||
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| Ligand Name: 3-(1,3-Benzodioxol-5-yl)-1-(3-nitrophenyl)prop-2-en-1-one | Ligand Info | |||||
| Structure Description | Structure of the Plasmodium falciparum falcipain 2 protease in complex with an (E)-chalcone inhibitor. | PDB:6SSZ | ||||
| Method | X-ray diffraction | Resolution | 3.45 Å | Mutation | Yes | [5] |
| PDB Sequence |
PQMNYEEVIK
-8 KYRGEENFDH2 AAYDWRLHSG12 VTPVKDQKNC22 GSAWAFSSIG32 SVESQYAIRK 42 NKLITLSEQE52 LVDCSFKNYG62 CNGGLINNAF72 EDMIELGGIC82 PDGDYPYVSD 92 APNLCNIDRC102 TEKYGIKNYL112 SVPDNKLKEA122 LRFLGPISIS132 VAVSDDFAFY 142 KEGIFDGECG152 DQLNHAVMLV162 GFGMKEIVNP172 LTKKGEKHYY182 YIIKNSWGQQ 192 WGERGFINIE202 TDESGLMRKC212 GLGTDAFIPL222 I
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| Ligand Name: amino{[4-({N-[(2S)-3-carboxy-2-hydroxypropanoyl]-L-leucyl}amino)butyl]amino}methaniminium | Ligand Info | |||||
| Structure Description | Crystal Structure of Falcipain-2 with Its inhibitor, E64 | PDB:3BPF | ||||
| Method | X-ray diffraction | Resolution | 2.90 Å | Mutation | No | [6] |
| PDB Sequence |
QMNYEEVIKK
10 YRGEENFDHA20 AYDWRLHSGV30 TPVKDQKNCG40 SCWAFSSIGS50 VESQYAIRKN 60 KLITLSEQEL70 VDCSFKNYGC80 NGGLINNAFE90 DMIELGGICP100 DGDYPYVSDA 110 PNLCNIDRCT120 EKYGIKNYLS130 VPDNKLKEAL140 RFLGPISISV150 AVSDDFAFYK 160 EGIFDGECGD170 QLNHAVMLVG180 FGMKEIVNGE195 KHYYYIIKNS205 WGQQWGERGF 215 INIETDESGL225 MRKCGLGTDA235 FIPLIE
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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 Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 1 | Novel molecular targets for antimalarial drug development. Chem Biol Drug Des. 2008 Apr;71(4):287-97. | |||||
| REF 2 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800004280) | |||||
| REF 3 | A prodomain peptide of Plasmodium falciparum cysteine protease (falcipain-2) inhibits malaria parasite development. J Med Chem. 2008 Jun 12;51(11):3116-23. | |||||
| REF 4 | Opportunities and challenges in antiparasitic drug discovery. Nat Rev Drug Discov. 2005 Sep;4(9):727-40. | |||||
| REF 5 | The complex of Plasmodium falciparum falcipain-2 protease with an (E)-chalcone-based inhibitor highlights a novel, small, molecule-binding site. Malar J. 2019 Dec 2;18(1):388. | |||||
| REF 6 | Structures of falcipain-2 and falcipain-3 bound to small molecule inhibitors: implications for substrate specificity. J Med Chem. 2009 Feb 12;52(3):852-7. | |||||
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