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3EDQ

Crystal structure of Caspase-3 with inhibitor AC-LDESD-CHO

Summary for 3EDQ
Entry DOI10.2210/pdb3edq/pdb
Related3EDL
DescriptorCaspase-3, AC-LDESD-CHO peptide, ... (4 entities in total)
Functional Keywordsenzyme catalysis, cysteine protease, apoptosis, s-nitrosylation, thiol protease, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
Biological sourceHomo sapiens (Human)
More
Cellular locationCytoplasm: P42574 P42574
Total number of polymer chains6
Total formula weight59933.93
Authors
Fu, G. (deposition date: 2008-09-03, release date: 2008-10-28, Last modification date: 2024-11-13)
Primary citationFu, G.,Chumanevich, A.A.,Agniswamy, J.,Fang, B.,Harrison, R.W.,Weber, I.T.
Structural basis for executioner caspase recognition of P5 position in substrates.
Apoptosis, 13:1291-1302, 2008
Cited by
PubMed Abstract: Caspase-3, -6 and -7 cleave many proteins at specific sites to induce apoptosis. Their recognition of the P5 position in substrates has been investigated by kinetics, modeling and crystallography. Caspase-3 and -6 recognize P5 in pentapeptides as shown by enzyme activity data and interactions observed in the crystal structure of caspase-3/LDESD and in a model for caspase-6. In caspase-3 the P5 main-chain was anchored by interactions with Ser209 in loop-3 and the P5 Leu side-chain interacted with Phe250 and Phe252 in loop-4 consistent with 50% increased hydrolysis of LDEVD relative to DEVD. Caspase-6 formed similar interactions and showed a preference for polar P5 in QDEVD likely due to interactions with polar Lys265 and hydrophobic Phe263 in loop-4. Caspase-7 exhibited no preference for P5 residue in agreement with the absence of P5 interactions in the caspase-7/LDESD crystal structure. Initiator caspase-8, with Pro in the P5-anchoring position and no loop-4, had only 20% activity on tested pentapeptides relative to DEVD. Therefore, caspases-3 and -6 bind P5 using critical loop-3 anchoring Ser/Thr and loop-4 side-chain interactions, while caspase-7 and -8 lack P5-binding residues.
PubMed: 18780184
DOI: 10.1007/s10495-008-0259-9
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (1.61 Å)
Structure validation

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