PDBsum entry: 1i51

Hydrolase/hydrolase inhibitor

PDB id: 1i51

Contents

Protein chains

139 a.a. *

92 a.a. *

18 a.a. *

* Residue conservation analysis

PDB id:

1i51

Name:

Hydrolase/hydrolase inhibitor

Title:

Crystal structure of caspase-7 complexed with xiap

Structure:

Caspase-7 subunit p20. Chain: a, c. Engineered: yes. Mutation: yes. Caspase-7 subunit p11. Chain: b, d. Engineered: yes. X-linked inhibitor of apotosis protein. Chain: e, f.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: casp7. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Gene: xiap.

Biol. unit:

Dodecamer (from PQS)

Resolution:

2.45Å R-factor: 0.233 R-free: 0.272

Authors:

J.Chai,Y.Shi

Key ref:

J.Chai et al. (2001). Structural basis of caspase-7 inhibition by XIAP. Cell, 104, 769-780. PubMed id: 11257230 DOI: 10.1016/S0092-8674(01)00272-0

Date:

23-Feb-01 Release date: 23-Feb-02

Protein chains

P55210  (CASP7_HUMAN) -  Caspase-7

Seq: 303 a.a.

Struc: 139 a.a.*

Protein chains

P55210  (CASP7_HUMAN) -  Caspase-7

Seq: 303 a.a.

Struc: 92 a.a.

Protein chains

P98170  (XIAP_HUMAN) -  Baculoviral IAP repeat-containing protein 4

Seq: 497 a.a.

Struc: 18 a.a.

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

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

 Gene Ontology (GO) functional annotation 

• Cellular component: intracellular (2 terms)
• Biological process: apoptosis (2 terms)
• Biochemical function: cysteine-type peptidase activity (2 terms)

DOI no: 10.1016/S0092-8674(01)00272-0

Cell 104:769-780 (2001)

PubMed id: 11257230

Structural basis of caspase-7 inhibition by XIAP.

J.Chai, E.Shiozaki, S.M.Srinivasula, Q.Wu, P.Datta, E.S.Alnemri, Y.Shi, P.Dataa.

ABSTRACT

The inhibitor of apoptosis (IAP) proteins suppress cell death by inhibiting the catalytic activity of caspases. Here we present the crystal structure of caspase-7 in complex with a potent inhibitory fragment from XIAP at 2.45 A resolution. An 18-residue XIAP peptide binds the catalytic groove of caspase-7, making extensive contacts to the residues that are essential for its catalytic activity. Strikingly, despite a reversal of relative orientation, a subset of interactions between caspase-7 and XIAP closely resemble those between caspase-7 and its tetrapeptide inhibitor DEVD-CHO. Our biochemical and structural analyses reveal that the BIR domains are dispensable for the inhibition of caspase-3 and -7. This study provides a structural basis for the design of the next-generation caspase inhibitors.

Selected figure(s)

Figure 2.

Figure 3.
Figure 3. Specific Recognition of Caspase-7 by XIAP(A) Overall view of the catalytic groove on caspase-7, represented by its surface in cyan, and the bound XIAP fragment in pink. The important residues in XIAP are highlighted in yellow (Leu141, Val146, Val147, Asp148, and Ile149). The same XIAP/caspase-7 orientation is maintained for panels (B) and (C). This panel was prepared using GRASP (Nicholls et al., 1991). (B) Overall view of the interface highlighting the four loops that constitute the catalytic groove. Caspase-7 and XIAP are shown in green and pink, respectively. The side chains of the critical contact residues in XIAP are labeled and shown in orange. The coloring scheme is the same for panels (C) and (D). (C) Stereo view of the hydrophobic interface involving a short α helix and the N-terminal half of the extended segment from XIAP. To avoid congestion, only those critical contact residues that are not labeled in panel (B) are labeled here. (D) Stereo view of the hydrophilic interface involving the C-terminal half of the extended XIAP segment. Hydrogen bonds are represented by red dashed lines

The above figures are reprinted by permission from Cell Press: Cell (2001, 104, 769-780) copyright 2001.

Figures were selected by the author.