Table 2.
Changes in betweenness centrality (BC): Table of residues showing significant changes in average BC (ΔBC) due to mutation (pyrimethamine-free: WT-free less mutant-free; pyrimethamine-bound: WT-PYR less mutant-PYR) and pyrimethamine binding (PYR-free less PYR-bound). In bold are residues showing changes in BC at sites with high centrality, while ↑ and ↓ signify residues with significant positive and negative ΔBC values, respectively, obtained by using a threshold value of +/−2 SD of the ΔBC values for each system. Positive ΔBC signify decrease in residue connectivity while negative ΔBC stands for increased residue connectivity and hence increased residue participation in communication.
| Effect of Mutation (pyrimethamine-free: WT-free less mutant-free) | ||
|---|---|---|
| Protein | ΔBC | Residues |
| S108N | ↑ | Ala13, Ala16, Cys18, Gly41, Tyr158, Tyr159, Gly165, Ser167, Thr185 |
| ↓ | Ile14, Tyr35, Thr36, Ile143, Lys160, Val168, Gln171, Pro198, Asn201 | |
| N51I_S108N | ↑ | Gly41, Gly165, Ser167, Thr185 |
| ↓ | Lys23, Asp91, Asn157, Gln171, Pro198 | |
| C59R_S108N | ↑ | Lys49, Cys78, Lys79, Gly165, Thr185, Phe196 |
| ↓ | Thr36, Asn51, Asp81, Arg106, Lys132, Asn157, Val168, Gln171, Ile200 | |
| N51I_C59R_S108N | ↑ | Ala16, Cys18, Glu21, Gly41, Val103, Gly165, Ser167 |
| ↓ | Phe32, Asn33, Tyr35, Lys96, Val168, Gln171, Pro198 | |
| C59R_S108N_I164L | ↑ | Ala13, Cys15, Gly41, Tyr158, Gly166, Thr185, Phe196 |
| ↓ | Ser22, Glu71, Lys72, Lys160, Gln171, Lys181, Pro198 | |
| N51I_C59R_S108N_I164L | ↑ | Ile11, Gly41, Lys79, Tyr158, Gly165, Ser167, Thr185, Phe196 |
| ↓ | Ser22, Ser95, Ile112, Asn124, Val168, Gln171, Pro198 | |
| Effect of Mutation (pyrimethamine-bound: WT-PYR less mutant-PYR) | ||
| S108N | ↑ | Cys17, Gly26, Leu46, Cys78, Gly105, Trp109, Gly165, Gly166 |
| ↓ | Lys97, Val101, Ser167, Val168, Tyr170, Gln171 | |
| N51I_S108N | ↑ | Cys17, Leu46, Pro47, Met55, Gly105, Gly166, Leu174 |
| ↓ | Glu21, Gly41, Tyr158, Tyr159, Ser167, Tyr170, Gln171 | |
| C59R_S108N | ↑ | Ile11, Cys17, Val20, Leu46, Pro47, Gly105, Trp109, Gly165 |
| ↓ | Asn24, Phe32, Thr36, Lys97, Ser167, Val168, Tyr170, Gln171 | |
| N51I_C59R_S108N | ↑ | Cys17, Leu46, Pro47, Gly105, Trp109 |
| ↓ | Cys15, Tyr35, Gly41, Ser167, Val168, Lys180, Asn201 | |
| C59R_S108N_I164L | ↑ | Ala16, Cys17, Leu46, Pro47, Met55, Arg59, Gly105, Trp109, Gly165, Lys181 |
| ↓ | Ser22, Ser167, Val168, Tyr170, Gln171, Pro198, Thr220 | |
| N51I_C59R_S108N_I164L | ↑ | Cys17, Val20, Leu46, Pro47, Gly105, Trp109, Gly165 |
| ↓ | Glu21, Gly41, Asn90, Ser167, Val168, Tyr170, Gln171, Lys180, Pro198 | |
| Effect of Pyrimethamine (PYR-free less PYR-bound) | ||
| WT | ↑ | Glu21, Gly41, Tyr158, Ser167, Tyr170, Glu175, Lys180, Asp194, Phe196 |
| ↓ | Cys17, Leu46, Pro47, Gly105, Pro198 | |
| S108N | ↑ | Asn24, Tyr35, Glu71, Cys78, Lys79, Lys160, Val168, Phe196, AS201 |
| ↓ | Lys23, Val89, Asn157, Tyr158, Tyr159, Gln171 | |
| N51I_S108N | ↑ | Lys23, Met55, Asp91, Ser95, Val103, Asn157, Gly166, Pro198 |
| ↓ | Gly41, Val45, Pro93, Leu98, Met104, Ser167 | |
| C59R_S108N | ↑ | Gly41, Asp81, Met81, Lys132, Ser167 |
| ↓ | Asn24, Val31, Phe32, Val45, Lys49, Ser81, Lys81, Lys97, Gln171, Pro198 | |
| N51I_C59R_S108N | ↑ | Asn33, Lys96, Asn157, Tyr159, Tyr170, Gln171, Pro198 |
| ↓ | Asp10, Cys15, Ser22, Lys23, Gly41, Ile163, Val168, Asn201 | |
| C59R_S108N_I164L | ↑ | Ile11, Ala16, Cys18, Lys23, Ser52, Arg59, Glu71, Lys72, Lys160, Gly165, Lys181 |
| ↓ | Asn34, Asn157, Ile163, Val168, Gln171, Ile182 | |
| N51I_C59R_S108N_I164L | ↑ | Ser22, Lys23, Lys27, Ser95, Lys96, Asn100, Lys155, Gly166, Tyr191 |
| ↓ | Thr36, Gly39, Asn90, Leu164, Pro198 | |