Peptide name : Dimeric Smac Mature Smac (1-4)

Source/Organism : SMAC

Linear/Cyclic : Linear

Chirality : L

Peptide length: 14

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 : HeLa

Cancer type : Not specified

Other activity : Not found

Amino acid composition bar chart :

Molecular mass : 1433.7375 Dalton

Aliphatic index : 1.257

Instability index : 51.6286

Hydrophobicity (GRAVY) : 0.4714

Isoelectric point : 10.003

Charge (pH 7) : 1.7939

Aromaticity : 0

Molar extinction coefficient (cysteine, cystine): (0, 0)

Hydrophobic/hydrophilic ratio : 2.5

hydrophobic moment : 0.04

Missing amino acid : C,R,W,H,T,M,E,F,S,D,Y,L,N,G

Most occurring amino acid : A

Most occurring amino acid frequency : 4

Least occurring amino acid : V

Least occurring amino acid frequency : 2

Secondary structure fraction (Helix, Turn, Sheet): (0.4, 0.1, 0.2)

SMILES Notation: CC[C@H](C)[C@H](NC(=O)[C@@H]1CCCN1C(=O)[C@@H](NC(=O)[C@H](C)N)C(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N1CCC[C@H]1C(=O)N[C@H](C(=O)N[C@@H](C)C(=O)O)C(C)C)[C@@H](C)CC

1 : Gao Z, et al. A dimeric Smac/diablo peptide directly relieves caspase-3 inhibition by XIAP. Dynamic and cooperative regulation of XIAP by Smac/Diablo. J Biol Chem. 2007; 282:30718-27. doi: 10.1074/jbc.M705258200

Paper title : A dimeric Smac/diablo peptide directly relieves caspase-3 inhibition by XIAP. Dynamic and cooperative regulation of XIAP by Smac/Diablo.

Doi : https://doi.org/10.1074/jbc.M705258200

Abstract : Caspase activation, the executing event of apoptosis, is under deliberate regulation. IAP proteins inhibit caspase activity, whereas Smac/Diablo antagonizes IAP. XIAP, a ubiquitous IAP, can inhibit both caspase-9, the initiator caspase of the mitochondrial apoptotic pathway, and the downstream effector caspases, caspase-3 and caspase-7. Smac neutralizes XIAP inhibition of caspase-9 by competing for binding of the BIR3 domain of XIAP with caspase-9, whereas how Smac liberates effector caspases from XIAP inhibition is not clear. It is generally believed that binding of Smac with IAP generates a steric hindrance that prevents XIAP from inhibiting effector caspases, and therefore small molecule mimics of Smac are not able to reverse inhibition of the effector caspases. Surprisingly, we show here that binding of a dimeric Smac N-terminal peptide with the BIR2 domain of XIAP effectively antagonizes inhibition of caspase-3 by XIAP. Further, we defined the dynamic and cooperative interaction of Smac with XIAP: binding of Smac with the BIR3 domain anchors the subsequent binding of Smac with the BIR2 domain, which in turn attenuates the caspase-3 inhibitory function of XIAP. We also show that XIAP homotrimerizes via its C-terminal Ring domain, making its inhibitory activity toward caspase-3 more susceptible to Smac.