PDBsum entry 4hqr

Hydrolase/hydrolase inhibitor

PDB id: 4hqr

Contents

Protein chains

217 a.a.

230 a.a.

Ligands

ACE-ASP-GLU-VAL-ASJ ×2

PDB id:

4hqr

Name:

Hydrolase/hydrolase inhibitor

Title:

Crystal structure of mutant form of caspase-7

Structure:

Caspase-7. Chain: a, b. Fragment: unp residues 47-303. Engineered: yes. Mutation: yes. Ac-asp-glu-val-asp-aldehyde. Chain: e, f. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes

Resolution:

3.00Å R-factor: 0.218 R-free: 0.253

Authors:

Y.Lee,H.J.Kang,K.-H.Bae,S.J.Kim,S.J.Chung

Key ref:

H.J.Kang et al. (2013). Structural asymmetry of procaspase-7 bound to a specific inhibitor. Acta Crystallogr D Biol Crystallogr, 69, 1514-1521. PubMed id: 23897474 DOI: 10.1107/S0907444913010196

Date:

26-Oct-12 Release date: 11-Sep-13

Protein chain

P55210  (CASP7_HUMAN) -  Caspase-7 from Homo sapiens

Seq: 303 a.a.

Struc: 217 a.a.

Protein chain

P55210  (CASP7_HUMAN) -  Caspase-7 from Homo sapiens

Seq: 303 a.a.

Struc: 230 a.a.

Enzyme reactions

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

DOI no: 10.1107/S0907444913010196

Acta Crystallogr D Biol Crystallogr 69:1514-1521 (2013)

PubMed id: 23897474

Structural asymmetry of procaspase-7 bound to a specific inhibitor.

H.J.Kang, Y.M.Lee, K.H.Bae, S.J.Kim, S.J.Chung.

ABSTRACT

Caspase-7 is expressed as a proenzyme and is activated by initiator caspases upon the transmission of cell-death signals. Despite extensive structural and biochemical analyses, many questions regarding the mechanism of caspase-7 activation remain unanswered. Caspase-7 is auto-activated during overexpression in Escherichia coli, even in the absence of initiator caspases, indicating that procaspase-7 has intrinsic catalytic activity. When variants of procaspase-7 with altered L2 loops were prepared, a variant with six inserted amino acids showed meaningful catalytic activity which was inhibited by Ac-DEVD-CHO. The kinetic constants of the procaspase-7 variant were determined and its three-dimensional structure was solved with and without bound inhibitor. The homodimeric procaspase-7 bound to the inhibitor revealed an asymmetry. One monomer formed a complete active site bound to the inhibitor in collaboration with the L2 loop from the other monomer, whereas the other monomer had an incomplete active site despite the bound inhibitor. Consequently, the two L2 loops in homodimeric procaspase-7 served as inherent L2 and L2' loops forming one complete active site. These data represent the first three-dimensional structure of a procaspase-7 variant bound to a specific inhibitor, Ac-DEVD-CHO, and provide insight into the folding mechanism during caspase-7 activation and the basal activity level of procaspase-7.