2OK9

PrTX-I-BPB

Summary for 2OK9

• Entry DOI: 10.2210/pdb2ok9/pdb
• Related: 1BK9 1GOD 1PA0 1QLL 1XXS 1Z76
• Descriptor: Phospholipase A2 homolog 1, p-Bromophenacyl bromide, ISOPROPYL ALCOHOL, ... (4 entities in total)
• Functional Keywords: prtx-i-bpb complex, lys49-pla2, bothrops pirajai, piratoxin i, toxin
• Biological source: Bothrops pirajai (Piraja's lance head)
• Total number of polymer chains: 2
• Total formula weight: 28184.27

Authors

Marchi-Salvador, D.P.,Fernandes, C.A.H.,Soares, A.M.,Fontes, M.R. (deposition date: 2007-01-16, release date: 2008-09-23, Last modification date: 2024-10-30)

Primary citation

Marchi-Salvador, D.P.,Fernandes, C.A.,Silveira, L.B.,Soares, A.M.,Fontes, M.R.
Crystal structure of a phospholipase A(2) homolog complexed with p-bromophenacyl bromide reveals important structural changes associated with the inhibition of myotoxic activity.
Biochim.Biophys.Acta, 1794:1583-1590, 2009

PubMed Abstract: For the first time, the structure of a catalytic inactive phospholipase A(2) homolog (Lys49-PLA(2)s) complexed with p-bromophenacyl bromide (BPB) has been solved by X-ray crystallography. Lys49-PLA(2)s are among the main components of Viperidae snake venoms, causing myonecrosis and other actions despite their catalytic inactivity. BPB, a classic inhibitor of catalytic-active PLA(2)s, has been used since the 1970s because it binds specifically the His48 residue of the catalytic site. Curiously, when Lys49-PLA(2) is chemically modified by BPB, it causes a partial inhibition of the myotoxic function which is associated with the C-terminus and not with the catalytic site. The structure of PrTX-I complexed to BPB revealed unambiguously that the inhibitor binds covalently to His48, causing a distortion of the Ca(2)(+)-binding loop region and C-terminus rearrangement in one of its monomers. The comparison between the apo and BPB-complexed PrTX-I structures showed an increased symmetry between the two monomers with the formation of an interchain hydrogen bond between Tyr119 residues. PrTX-I undergoes tertiary and quaternary structural changes when complexed to BPB which could be related to reduction of myotoxicity and other toxic activities. We also proposed a novel myotoxic inhibition hypothesis integrating "myotoxic" and "active" sites for bothropic Lys49-PLA(2)s.

PubMed: 19616648
DOI: 10.1016/j.bbapap.2009.07.005

Experimental method

X-RAY DIFFRACTION (2.34 Å)