# Structure, Biology, and Therapeutic Application of Toxin-Antitoxin Systems in Pathogenic Bacteria
## 4 Structural Characteristics of TA Proteins from Pathogenic Bacteria
### MazEf
\begin{table}
\begin{tabular}{c c c c c c} \hline \hline
**Pathogenic Bacteria** & **TA Protein** & \begin{tabular}{c} **Oligomeric State** \\ **(Stoichiometry)** \\ \end{tabular} & \begin{tabular}{c} **Pfan Annotation/** \\ **Accession ID** \\ \end{tabular} & \begin{tabular}{c} **PDB ID/** \\ **Deposit Date** \\ \end{tabular} & **Ref.** \\ \hline \multirow{4}{*}{\begin{tabular}{c} Myccheterrium \\ _tuberculosis_ \\ \end{tabular} } & \multirow{4}{*}{VapBC3 Complex} & Hetero-octamer (AB4) & VarpB3: Ribbon-helix-helix & \multirow{4}{*}{4 CHG/2013-12-02} & \multirow{4}{*}{[175]} \\  & & Hetero-octamer & Family/PP01402 & & \\  & & (AB4) & & VarC3: PIN & \\  & & & Domain/PP01850 & & \\ \hline \multirow{4}{*}{\begin{tabular}{c} Myccheterrium \\ _tuberculosis_ \\ \end{tabular} } & \multirow{4}{*}{VapBC15 Complex} & Hetero-octamer (AB2) & \begin{tabular}{c} VarpB15: Uncharacterized, \\ Conserved Protein/PP09957 \\ \end{tabular} & \multirow{4}{*}{4 CHG/2013-12-02} & \multirow{4}{*}{[175]} \\  & & & (AB2) & & \\  & & & Domain/PP10850 & & \\ \hline \multirow{4}{*}{\begin{tabular}{c} Myccheterrium \\ _tuberculosis_ \\ \end{tabular} } & \multirow{4}{*}{VapBC30 Complex} & Hetero-octamer (AB2) & \begin{tabular}{c} VarpB30: Rv6023-like \\ Transcription \\ Factor/PP0704 \\ \end{tabular} & \multirow{4}{*}{4 XGQ/2015-01-02} & \multirow{4}{*}{[176]} \\  & & & (AB2) & & \\  & & & & Domain/PP01850 & \\ \hline \multirow{4}{*}{\begin{tabular}{c} Myccheterrium \\ _tuberculosis_ \\ \end{tabular} } & \multirow{4}{*}{YeM Antitoxin} & Homo-tetramer (A4) & Antitoxin Phd\_YeM & \multirow{4}{*}{3 CTO/2008-04-14} & \multirow{4}{*}{[177]} \\  & & & & Domain/PP02604 & \\ \hline \multirow{4}{*}{\begin{tabular}{c} Bacillus subtilis \\ \end{tabular} } & \multirow{4}{*}{SpoIISA-SpoIISB & Hetero-tetramer (AB2)} & SpotISSA: Antitoxin SpoIISA & \multirow{4}{*}{30Q/2010-07-29} & \multirow{4}{*}{[178]} \\  & & & (AB2) & & Family/PP141471 & \\ \hline \multirow{4}{*}{\begin{tabular}{c} Bacillus subtilis \\ \end{tabular} } & \multirow{4}{*}{MazEf Complex} & Hetero-hexamer (AA82) & \begin{tabular}{c} MaE: Ribbon-helix-helix \\ Protein, CoPG \\ family/PP01402 \\ \end{tabular} & \multirow{4}{*}{4 MEF/2013-08-25} & \multirow{4}{*}{[179]} \\  & & & (AA82) & & \\ \hline \multirow{4}{*}{\
\begin{tabular}{c} Bacillus subtilis \\ \end{tabular} } & \multirow{4}{*}{MazF-Substrate & Homo-dimer (A2)} &
\begin{tabular}{c} MaE: Perm-like \\ Protein/FF02452 \\ \end{tabular} & \multirow{4}{*}{4 MDX/2013-08-23} & \multirow{4}{*}{[179]} \\  & & & & Substrate Sequence: & \\  & & UUdUACAUAA & & \\ \hline \hline \end{tabular}  
* This annotation is according to the CATH protein structure classification.  
\end{table} 
Table 2: _Cont_. of _B. subtilis_ MazF is highly similar to that of _E. coli_ MazF. The \(N\)-terminal domain of MazE contains \(\beta\)1 strand and \(\alpha\)1 helix followed by the \(N\)-terminal region of \(\alpha\)2 helix. This domain is responsible for dimerization, which forms a RHH motif for DNA binding. On the other hand, the \(C\)-terminal domain of MazE contains the \(C\)-terminal region of \(\alpha\)2 helix and the short \(\alpha\)3 helix, which bind tightly to a cleft formed by the dimerization of MazF. MazE prevents an RNase activity of MazF by sterically blocking the RNA binding channel of MazF. In contrast to the structural features of _B. subtilis_ MazE, _E. coli_ MazE contains the \(N\)-terminal \(\beta\) barrel core for DNA binding and the \(C\)-terminal long loop for MazF binding (Figure 2C). Consistent with the structural difference, _E. coli_ MazE cannot inhibit the toxicity of _B. subtilis_ MazF [180]. The MazF structures in complex with uncleavable substrate analogues from _B. subtilis_ and _E. coli_ are shown in Figure 2B,C. The structural comparison reveals that they have a common mode of substrate recognition on a large interaction surface [167]. However, the substrate binding of _E. coli_ MazF is achieved by fewer hydrogen bonds to specific RNA bases and poorer surface complementarity than that of _B.