5tfv

Crystal Structure of MT-I isolated from Bothrops asper venom.

spinqualitylabelsall models 5tfv, resolution 2.54Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5tfv is a 2 chain structure with sequence from Bothrops asper. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: TRS Activity: Phospholipase A(2), with EC number 3.1.1.4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [PA2B3_BOTAS] Snake venom phospholipase A2 (PLA2) that displays local myotoxic activity and induces a dose-dependent edema. Myotoxic activity is probably related to a molecular region different from the catalytic site, although enzymatic activity greatly enhances myotoxin action. PLA2 catalyzes the calcium-dependent hydrolysis of the 2-acyl groups in 3-sn-phosphoglycerides. Publication Abstract from PubMed Snake venoms from the Viperidae and Elapidae families often have several phospholipases A2 (PLA2s), which may display different functions despite having a similar structural scaffold. These proteins are considered an important target for the development of drugs against local myotoxic damage because they are not efficiently neutralized by conventional serum therapy. PLA2s from these venoms are generally divided into two classes: (i) catalytic PLA2s (or Asp49-PLA2s) and (ii) non-catalytic PLA2-like toxins (or Lys49-PLA2s). In many Viperidae venoms, a subset of the basic Asp49-PLA2s displays some functional and structural characteristics of PLA2-like proteins and group within the same phylogenetic clade, but their myotoxic mechanism is still largely unknown. In the present study, we have crystallized and solved the structure of myotoxin I (MT-I), a basic myotoxic Asp49-PLA2 isolated from Bothrops asper venom. The structure presents a dimeric conformation that is compatible with that of previous dimers found for basic myotoxic Asp49-PLA2s and Lys49-PLA2s and has been confirmed by other biophysical and bioinformatics techniques. This arrangement suggests a possible cooperative action between both monomers to exert myotoxicity via two different sites forming a putative membrane-docking site (MDoS) and a putative membrane disruption site (MDiS). This mechanism would resemble that proposed for Lys49-PLA2s, but the sites involved appear to be situated in a different region. Thus, as both sites are close to one another, they form a "myotoxic cluster", which is also found in two other basic myotoxic Asp49-PLA2s from Viperidae venoms. Such arrangement may represent a novel structural strategy for the mechanism of muscle damage exerted by the group of basic, Asp49-PLA2s found in viperid snake venoms. Crystal structure of a phospholipase A2 from Bothrops asper venom: Insights into a new putative "myotoxic cluster".,Salvador GH, Dos Santos JI, Lomonte B, Fontes MR Biochimie. 2017 Feb;133:95-102. doi: 10.1016/j.biochi.2016.12.015. Epub 2016 Dec , 27. PMID:28034717 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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