Disease relevance of MTX2

• Affinity-purified antibodies against metaxin 2 were prepared against the recombinant protein produced in E. coli and were used to analyze the subcellular distribution of metaxin 2 [1].
• These proteins share 80-90% sequence identity and showed structural similarity to bacterial toxins: mosquitocidal toxin (MTX2) from Bacillus sphaericus and alpha toxin from Clostridium septicum [2].
• The numbers of drop-outs due to toxicity were SSZ 9, MTX 2, COMBI 5 [3].

High impact information on MTX2

• The three-dimensional solution structure of the MTX2 toxin (65 amino acids and 4 disulfides) from the green mamba venom (Dendroaspis angusticeps), a toxin that activates the pharmacological M1 muscarinic acetylcholine receptors, has been determined by nuclear magnetic resonance and molecular modeling [4].
• For instance, the RMSd for the backbone atoms between MTX2 and the curaremimetic toxin alpha (from Naja nigricollis), the acetylcholinesterase inhibitor fasciculin 1 (from Dendroaspis angusticeps), and the cardiotoxic toxin gamma (from Naja nigricollis) are 1.86, 1.87, and 2.04 A, respectively [4].
• A particularly labile Asp-Pro bond in the green mamba muscarinic toxin MTX2. Effect of protein conformation on the rate of cleavage [5].
• Alkali extraction of mitochondria indicated that metaxin 2 is peripherally associated with mitochondrial membranes [1].
• In subcellular fractions of mouse liver, a 29 kD immunoreactive protein, consistent in size with the predicted translation product of metaxin 2 cDNA, was found solely in mitochondria [1].

Biological context of MTX2

• Among overexpressed proteins were heat-shock, structural and membrane proteins and enzymes involved in gene silencing, protein synthesis/degradation, mitochondrial protein import (metaxin 2), detoxification (GST-pi) and energy metabolism [6].

Anatomical context of MTX2

• In bone marrow cells, the combinations of 5-FU 2 h prior to MTX or MTX 2 h prior to 5-FU followed by a 48 h incubation, respectively, gave growth rates of 79.66 +/- 7.41% (protection) and 31.39 +/- 1.77% of the control rate [7].

Associations of MTX2 with chemical compounds

• The overall folding of MTX2 consists of three loops stabilized by the four disulfides and forming a two- and a three-stranded beta-sheet [4].
• The combinations of 5-FU 2 h prior to MTX or MTX 2 h prior to 5-FU followed by a 48 h incubation, respectively, gave growth rates of 20.96 +/- 2.44% and 19.86 +/- 2.56% of the control rate for MCF-7 cells [7].

Analytical, diagnostic and therapeutic context of MTX2

• Thereafter SR patients received HD-MTX 2 g/m2, a modified protocol II, and continuation therapy with triple intrathecal chemotherapy (TIT); IR patients received protocol Ib, HD-MTX 5 g/m2, protocol II and continuation therapy with TIT; HR patients received 9 polychemotherapy blocks, cranial irradiation and continuation therapy [8].

References