Peptide name : Bad a

Source/Organism : BH3-only, Sensizers (BAD, HRK, Noxa)

Linear/Cyclic : Linear

Chirality : L

Peptide length: 20

C-terminal modification: Linear

N-terminal modification : Not found

Non-natural peptide information: None

Assay type : Not specified

Assay time : Not found

Activity : Not found

Cell line : Not found

Cancer type : Not found

Other activity : Not found

Amino acid composition bar chart :

Molecular mass : 2483.8053 Dalton

Aliphatic index : 0.635

Instability index : 54.29

Hydrophobicity (GRAVY) : -0.96

Isoelectric point : 9.9708

Charge (pH 7) : 1.7663

Aromaticity : 0.15

Molar extinction coefficient (cysteine, cystine): (6990, 6990)

Hydrophobic/hydrophilic ratio : 0.81818181

hydrophobic moment : 0.4127

Missing amino acid : C,H,T,Q,P,I

Most occurring amino acid : R

Most occurring amino acid frequency : 4

Least occurring amino acid : N

Least occurring amino acid frequency : 1

Secondary structure fraction (Helix, Turn, Sheet): (0.3, 0.2, 0.3)

SMILES Notation: CSCC[C@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)CNC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@H](C(=O)N[C@@H](CC(=O)O)C(=O)O)C(C)C

1 : Fire E, et al. Mcl-1-Bim complexes accommodate surprising point mutations via minor structural changes. Protein Sci. 2010; 19:507-19. doi: 10.1002/pro.329

Paper title : Mcl-1-Bim complexes accommodate surprising point mutations via minor structural changes.

Doi : https://doi.org/10.1002/pro.329

Abstract : Mcl-1 is an antiapoptotic Bcl-2-family protein that protects cells against death. Structures of Mcl-1, and of other anti-apoptotic Bcl-2 proteins, reveal a surface groove into which the alpha-helical BH3 regions of certain proapoptotic proteins can bind. Despite high overall structural conservation, differences in this groove afford binding specificity that is important for the mechanism of Bcl-2 family function. We report the crystal structure of human Mcl-1 bound to a BH3 peptide derived from human Bim and the structures for three complexes that accommodate large physicochemical changes at conserved Bim sites. The mutations had surprisingly modest effects on complex stability, and the structures show that Mcl-1 can undergo small changes to accommodate the mutant ligands. For example, a shift in a leucine side chain fills a hole left by an isoleucine-to-alanine mutation at the first hydrophobic buried position of Bim BH3. Larger changes are also observed, with shifting of helix alpha3 accommodating an isoleucine-to-tyrosine mutation at this same position. We surveyed the variation in available Mcl-1 and Bcl-x(L) structures and observed moderate flexibility that is likely critical for facilitating interactions of diverse BH3-only proteins with Mcl-1. With the antiapoptotic Bcl-2 family members attracting significant attention as therapeutic targets, these structures contribute to our growing understanding of how specificity is achieved and can help to guide the design of novel inhibitors that target Mcl-1.