PDBsum entry 3ibc

Hydrolase, apoptosis

PDB id: 3ibc

Contents

Protein chains

140 a.a. *

92 a.a. *

Ligands

ACE-TYR-VAL-ALA-ASP ×2

Waters ×59

* Residue conservation analysis

PDB id:

3ibc

Name:

Hydrolase, apoptosis

Title:

Crystal structure of caspase-7 incomplex with acetyl-yvad-cho

Structure:

Caspase-7. Chain: a, c. Fragment: p20 subunit. Synonym: casp-7, ice-like apoptotic protease 3, ice-lap3, apoptotic protease mch-3, cmh-1, caspase-7 subunit p20, caspase-7 subunit p11. Engineered: yes. Caspase-7. Chain: b, d. Fragment: p10 subunit.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: casp7, mch3. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Other_details: the peptide was obtained by chemical synthesis.

Resolution:

2.75Å R-factor: 0.203 R-free: 0.242

Authors:

J.Agniswamy

Key ref:

J.Agniswamy et al. (2009). Conformational similarity in the activation of caspase-3 and -7 revealed by the unliganded and inhibited structures of caspase-7. Apoptosis, 14, 1135-1144. PubMed id: 19655253

Date:

15-Jul-09 Release date: 01-Sep-09

Protein chains

P55210  (CASP7_HUMAN) -  Caspase-7 from Homo sapiens

Seq: 303 a.a.

Struc: 140 a.a.

Protein chains

P55210  (CASP7_HUMAN) -  Caspase-7 from Homo sapiens

Seq: 303 a.a.

Struc: 92 a.a.

Enzyme reactions

• Enzyme class: Chains A, B, C, D: E.C.3.4.22.60 - caspase-7.

Apoptosis 14:1135-1144 (2009)

PubMed id: 19655253

Conformational similarity in the activation of caspase-3 and -7 revealed by the unliganded and inhibited structures of caspase-7.

J.Agniswamy, B.Fang, I.T.Weber.

ABSTRACT

Caspase-mediated apoptosis has important roles in normal cell differentiation and aging and in many diseases including cancer, neuromuscular disorders and neurodegenerative diseases. Therefore, modulation of caspase activity and conformational states is of therapeutic importance. We report crystal structures of a new unliganded conformation of caspase-7 and the inhibited caspase-7 with the tetrapeptide Ac-YVAD-Cho. Different conformational states and mechanisms for substrate recognition have been proposed based on unliganded structures of the redundant apoptotic executioner caspase-3 and -7. The current study shows that the executioner caspase-3 and -7 have similar conformations for the unliganded active site as well as the inhibitor-bound active site. The new unliganded caspase-7 structure exhibits the tyrosine flipping mechanism in which the Tyr230 has rotated to block entry to the S2 binding site similar to the active site conformation of unliganded caspase-3. The inhibited structure of caspase-7/YVAD shows that the P4 Tyr binds the S4 region specific to polar residues at the expense of a main chain hydrogen bond between the P4 amide and carbonyl oxygen of caspase-7 Gln 276, which is similar to the caspase-3 complex. This new knowledge of the structures and conformational states of unliganded and inhibited caspases will be important for the design of drugs to modulate caspase activity and apoptosis.