dbacp01692
General Description
Peptide name : BIM EL-CTS
Source/Organism : BH3-only, Direct activators, BIM analogues
Linear/Cyclic : Linear
Chirality : L
Sequence Information
Sequence : PQMVILQLLRFIFRLVWRRH
Peptide length: 20
C-terminal modification: Linear
N-terminal modification : Not found
Non-natural peptide information: None
Activity Information
Assay type : Not specified
Assay time : Not found
Activity : Not found
Cell line : Not found
Cancer type : Breast cancer
Other activity : Not found
Physicochemical Properties
Amino acid composition bar chart :
Molecular mass : 2622.2321 Dalton
Aliphatic index : 1.46
Instability index : 92.96
Hydrophobicity (GRAVY) : 0.47
Isoelectric point : 12
Charge (pH 7) : 4.0457
Aromaticity : 0.15
Molar extinction coefficient (cysteine, cystine): (5500, 5500)
Hydrophobic/hydrophilic ratio : 1.85714285
hydrophobic moment : 0.9898
Missing amino acid : C,T,E,K,S,D,Y,N,A,G
Most occurring amino acid : L
Most occurring amino acid frequency : 4
Least occurring amino acid : P
Least occurring amino acid frequency : 1
Structural Information
3D structure :
Secondary structure fraction (Helix, Turn, Sheet): (0.2, 0.0, 0.5)
SMILES Notation: CC[C@H](C)[C@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H]1CCCN1)C(C)C)[C@@H](C)CC)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1c[nH]cn1)C(=O)O)C(C)C
Secondary Structure :
| Method | Prediction |
|---|---|
| GOR | CHHHHHHHHHHHHHHHHHHH |
| Chou-Fasman (CF) | EEEEECCCEEEEEEEECCCC |
| Neural Network (NN) | CCHHHHHHHHHHHHHHHHHC |
| Joint/Consensus | CCHHHHHHHHHHHHHHHHHC |
Molecular Descriptors and ADMET Properties
Molecular Descriptors: Click here to download
ADMET Properties: Click here to download
Cross Referencing databases
Reference
1 : Liu Q, et al. Bim escapes displacement by BH3-mimetic anti-cancer drugs by double-bolt locking both Bcl-XL and Bcl-2. Elife. 2019; 8:(unknown pages). doi: 10.7554/eLife.37689
Literature
Paper title : Bim escapes displacement by BH3-mimetic anti-cancer drugs by double-bolt locking both Bcl-XL and Bcl-2.
Doi : https://doi.org/10.7554/eLife.37689
Abstract : Tumor initiation, progression and resistance to chemotherapy rely on cancer cells bypassing programmed cell death by apoptosis. We report that unlike other pro-apoptotic proteins, Bim contains two distinct binding sites for the anti-apoptotic proteins Bcl-XL and Bcl-2. These include the BH3 sequence shared with other pro-apoptotic proteins and an unexpected sequence located near the Bim carboxyl-terminus (residues 181-192). Using automated Fluorescence Lifetime Imaging Microscopy - Fluorescence Resonance Energy Transfer (FLIM-FRET) we show that the two binding interfaces enable Bim to double-bolt lock Bcl-XL and Bcl-2 in complexes resistant to displacement by BH3-mimetic drugs currently in use or being evaluated for cancer therapy. Quantifying in live cells the contributions of individual amino acids revealed that residue L185 previously thought involved in binding Bim to membranes, instead contributes to binding to anti-apoptotic proteins. This double-bolt lock mechanism has profound implications for the utility of BH3-mimetics as drugs. .