2XYH

Caspase-3:CAS60254719

Summary for 2XYH

• Entry DOI: 10.2210/pdb2xyh/pdb
• Related: 1CP3 1GFW 1I3O 1NME 1NMQ 1NMS 1PAU 1QX3 1RE1 1RHJ 1RHK 1RHM 1RHQ 1RHR 1RHU 2C1E 2C2K 2C2M 2C2O 2CDR 2CJX 2CJY 2CNK 2CNL 2CNN 2CNO 2DKO 2J30 2J31 2J32 2J33 2XYG
• Descriptor: CASPASE-3 SUBUNIT P17, CASPASE-3 SUBUNIT P12, 5-CHLORO-4-OXOPENTANOIC ACID, ... (4 entities in total)
• Functional Keywords: hydrolase, in silico screening, docking, apoptosis
• Biological source: HOMO SAPIENS (HUMAN); More
• Cellular location: Cytoplasm: P42574 P42574
• Total number of polymer chains: 2
• Total formula weight: 27692.04

Authors

Ganesan, R.,Jelakovic, S.,Grutter, M.G.,Mittl, P.R. (deposition date: 2010-11-17, release date: 2011-08-17, Last modification date: 2024-10-23)

Primary citation

Ganesan, R.,Jelakovic, S.,Mittl, P.R.,Caflisch, A.,Grutter, M.G.
In Silico Identification and Crystal Structure Validation of Caspase-3 Inhibitors without a P1 Aspartic Acid Moiety.
Acta Crystallogr.,Sect.F, 67:842-, 2011

PubMed Abstract: Using a fragment-based docking procedure, several small-molecule inhibitors of caspase-3 were identified and tested and the crystal structures of three inhibitor complexes were determined. The crystal structures revealed that one inhibitor (NSC 18508) occupies only the S1 subsite, while two other inhibitors (NSC 89167 and NSC 251810) bind only to the prime part of the substrate-binding site. One of the major conformational changes observed in all three caspase-3-inhibitor complexes is a rotation of the Tyr204 side chain, which blocks the S2 subsite. In addition, the structural variability of the residues shaping the S1-S4 as well as the S1' subsites supports an induced-fit mechanism for the binding of the inhibitors in the active site. The high-resolution crystal structures reported here provide novel insights into the architecture of the substrate-binding site, which might be useful for the design of more potent caspase inhibitors.

PubMed: 21821879
DOI: 10.1107/S1744309111018604

Experimental method

X-RAY DIFFRACTION (1.89 Å)