1Z76

Crystal structure of an acidic phospholipase A2 (BthA-I) from Bothrops jararacussu venom complexed with p-bromophenacyl bromide

Summary for 1Z76

• Entry DOI: 10.2210/pdb1z76/pdb
• Related: 1u73 1umv
• Descriptor: phospholipase A2, p-Bromophenacyl bromide (3 entities in total)
• Functional Keywords: acidic phospholipase a2, bothrops jararacussu venom, platelet aggregation and hypotensive effects, oligomeric state, dimeric phospholipase a2, phospholipase a2 inhibition, p-bromophenacyl bromide, hydrolase
• Biological source: Bothrops jararacussu (jararacussu)
• Total number of polymer chains: 2
• Total formula weight: 27956.78

Authors

Magro, A.J.,Takeda, A.A.,Soares, A.M.,Fontes, M.R. (deposition date: 2005-03-24, release date: 2006-03-21, Last modification date: 2024-10-16)

Primary citation

Magro, A.J.,Takeda, A.A.,Soares, A.M.,Fontes, M.R.
Structure of BthA-I complexed with p-bromophenacyl bromide: possible correlations with lack of pharmacological activity.
Acta Crystallogr.,Sect.D, 61:1670-1677, 2005

PubMed Abstract: The crystal structure of an acidic phospholipase A(2) isolated from Bothrops jararacussu venom (BthA-I) chemically modified with p-bromophenacyl bromide (BPB) has been determined at 1.85 Angstroms resolution. The catalytic, platelet-aggregation inhibition, anticoagulant and hypotensive activities of BthA-I are abolished by ligand binding. Electron-density maps permitted unambiguous identification of inhibitor covalently bound to His48 in the substrate-binding cleft. The BthA-I-BPB complex contains three structural regions that are modified after inhibitor binding: the Ca(2+)-binding loop, beta-wing and C-terminal regions. Comparison of BthA-I-BPB with two other BPB-inhibited PLA(2) structures suggests that in the absence of Na(+) ions at the Ca(2+)-binding loop, this loop and other regions of the PLA(2)s undergo structural changes. The BthA-I-BPB structure reveals a novel oligomeric conformation. This conformation is more energetically and conformationally stable than the native structure and the abolition of pharmacological activities by the ligand may be related to the oligomeric structural changes. A residue of the ;pancreatic' loop (Lys69), which is usually attributed as providing the anticoagulant effect, is in the dimeric interface of BthA-I-BPB, leading to a new hypothesis regarding the abolition of this activity by BPB.

PubMed: 16301802
DOI: 10.1107/S0907444905029598

Experimental method

X-RAY DIFFRACTION (1.85 Å)