3I3I

Crystal Structure of Bothropstoxin-I crystallized at 283 K

Summary for 3I3I

• Entry DOI: 10.2210/pdb3i3i/pdb
• Related: 2OK9 2OQD 2QOG 3I3H
• Descriptor: Phospholipase A2 homolog bothropstoxin-1 (2 entities in total)
• Functional Keywords: homologue phospholipase a2, bothropstoxin-i, bthtx-i_10c, lys49-pla2 from bothrops jararacussu, snake venom, antibiotic, antimicrobial, disulfide bond, myotoxin, secreted, toxin
• Biological source: Bothrops jararacussu (Jararacussu)
• Cellular location: Secreted: Q90249
• Total number of polymer chains: 1
• Total formula weight: 13753.14

Authors

Salvador, G.H.M.,Marchi-Salvador, D.P.,Soares, A.M.,Fontes, M.R.M. (deposition date: 2009-06-30, release date: 2010-04-28, Last modification date: 2024-11-27)

Primary citation

Fernandes, C.A.,Marchi-Salvador, D.P.,Salvador, G.M.,Silva, M.C.,Costa, T.R.,Soares, A.M.,Fontes, M.R.
Comparison between apo and complexed structures of bothropstoxin-I reveals the role of Lys122 and Ca(2+)-binding loop region for the catalytically inactive Lys49-PLA(2)s.
J.Struct.Biol., 171:31-43, 2010

PubMed Abstract: Phospholipases A(2) (Asp49-PLA(2)s) are enzymes responsible for cellular membrane disruption through Ca(2+)-dependent hydrolysis of phospholipids. A class of these proteins (Lys49-PLA(2)s) does not show catalytic activity but can exert a pronounced local myotoxic effect that is not neutralized by serum therapy. In this work, we present five structures of Lys49-PLA(2)s from snakes of the Bothrops genus in apo form, complexed with PEG molecules and chemically modified by p-bromofenacil bromide (BPB), a classic inhibitor of PLA(2). We present herein an extensive structural analysis including: (i) the function of hydrophobic long-chain molecules as Lys49-PLA(2)s inhibitors, (ii) the role of Lys122, previously indicated as being responsible for Lys49-PLA(2)s catalytic inactivity and, (iii) a structural comparison of the Ca(2+)-binding loop region between Lys49 and Asp49-PLA(2)s. The Lys122 analysis of 30 different monomers for apo and complexed Lys49-PLA(2)s structures shows that this residue is very flexible and may bind to different carboxyl groups giving stability to the crystal structures. The structural comparisons of the Ca(2+)-binding loop region between Lys49 and Asp49-PLA(2)s reveal the importance of the Tyr28 residue conservation in Asp49-PLA(2)s to the integrity of this loop. The Tyr28 residue stabilizes this region by an interaction with Gly35 residue. In Lys49-PLA(2)s and low-catalytic Asp49-PLA(2)s this interaction does not occur, preventing the binding of Ca(2+).

PubMed: 20371382
DOI: 10.1016/j.jsb.2010.03.019

Experimental method

X-RAY DIFFRACTION (1.82 Å)