NB113 is an antitumor drug that belongs to the class of cycloselenols. This compound has been used in the treatment of hepatitis and cancer. It is also used in the treatment of arthritis and rheumatism. It binds to the receptor rStx2aB. It has a neutralization capacity.
The molecular structure is a big deal and it affects the properties and interactions of the molecule. This article will explore the structure of Nb113, the molecule that can provide a basis for neutralizing the nefarious Stx2a.
The molecular structure is a result of the Schrodinger equation, which describes the motion of electrons within the nucleus of the molecule. To derive the optimum molecular shape, we need to understand the properties of the molecule, which are mainly governed by the bond angles and valence. We can also calculate the strength of the bonds in the molecule, which is dependent on valence. The molecular structure of Nb113 was derived using X-ray crystallography.
A single bond in a carbonate molecule (H3CCH3) is a trippy affair. It has one tetrahedral carbon atom, and two octahedral carbon atoms, each separated by an abysmal eight-unit distance.
Using crystallography, we have determined the structure of Nb113 in complex with rStx2aB. This structure provides a structural basis for the neutralization of Stx2a holotoxin. Nb113 binds to the rStx2aB pentamer in a largely Gb3-receptor site. Its binding is mediated by residues in the framework regions of the pentamer. The interacting residues are indicated in stick representation.
Nb113-rStx2aB crystals were sensitive to beam exposure. After cryocooling, they lost diffractive power fast. This indicated a higher affinity for beam exposure. However, the outcome is more complex under experimental conditions. Nb113 and rStx2aB were found to bind with nanomolar affinity.
The epitopes of Nb113 and rStx2aB pentamer overlap. In the case of the Nb1132 construct, the Arg59 of Nb113 binds to amino acids of rStx2aB pentamer. These residues engage in salt bridges. This results in a competitive interaction between Nb113 and the pentamer.
Interactions with rStx2aB
X-ray crystallography analysis of the Nb113-rStx2aB complex revealed that five Nb113 molecules are bound to a pentameric Stx2a B5 domain. This reveals the structural basis for the neutralization of Stx2a.
The crystallization conditions were optimized in two ways. First, the crystallization conditions were screened using the hanging-drop vapor-diffusion method. The rStx2aB-Nb113 complex was then concentrated using a 5000 MWCO concentrator. This method allowed us to determine the molecular mass of the Nb113-rStx2aB complex, which is 12.8 mg/mL.
Second, we used SPR to determine which Nb pairs were competing for overlapping epitopes. SPR is a very elegant technique for epitope binning. This was used to identify the Nbs that compete for overlapping epitopes on the biotinylated rStx2aB pentamer.
The resulting sensor grams were fitted to a 1:1 Langmuir binding model. This model was used to fit data from three flow cells of a single biosensor chip.
NB113 is a bivalent Nb that is used as a toxin neutralizer. Its structure has been determined using X-ray crystallography. This structure revealed that the epitope of Nb113 overlapped with the binding site of Gb3, which is a receptor for rStx2aB. This resulted in a structural basis for the neutralization of Stx2a by Nb113.
Nb113's toxin-neutralizing potential was compared with that of the monovalent version of NB113. The results showed that the tandem-repeated bivalent Nb1132 had a higher toxin neutralization capacity than the monovalent version. These results indicate that the fusion of bivalent Nb1132 with serum albumin-specific Nb has high toxin neutralization potential and prolonged blood circulation. Hence, a fusion of bivalent Nb1132 and serum albumin-specific Nb may be an efficient approach to produce toxin neutralizers that are capable of combining high toxin neutralization capacity with prolonged blood circulation.