Table 2.
Summary of congenital ChAT mutations
| Amino-acid change (human) | Corresponding residue (rat) | Effect on ChAT activity | Reference | Likely structural effect of mutation |
|---|---|---|---|---|
| V194L | V86 | ND | Maselli et al (2003) | Alter AcCoA- and choline-binding sites |
| L210P | L102 | ↑↑Km AcCoA, ↑↑Km chol, ↓kcat | Ohno et al (2001) and Maselli et al (2003) | Alter active site and choline-binding site |
| P211A | P103 | ↑↑Km AcCoA, ↑kcat | Ohno et al (2001) and Maselli et al (2003) | Alter active site and choline-binding site |
| I305T | I197 | ↑Km AcCoA, ↓E | Ohno et al (2001) | Destabilize fold, distant from active and binding sites |
| I336T | I228 | ND | Schmidt et al (2003) | Destabilize fold, distant from active and binding sites |
| R420C | R312 | ↑↑Km AcCoA, ↑↑Km chol, ↑kcat, ↓E | Ohno et al (2001) | Destabilize fold, distant from active and binding sites |
| E441K | E333 | No activity, ↓E | Ohno et al (2001) | Alter active site and choline-binding site |
| R482G | R374 | ↑Km AcCoA | Ohno et al (2001) | Alter extended open coil, distant from binding sites |
| S498L | S390 | ↑Km AcCoA | Ohno et al (2001) | Effect not apparent, distant from active and binding sites |
| V506L | V398 | ↑Km AcCoA | Ohno et al (2001) and Maselli et al (2003) | Effect not apparent, distant from active and binding sites |
| R560H | R452 | ↑↑Km AcCoA, ↑↑Km chol ↓kcat | Ohno et al (2001) | Alter AcCoA-binding site |
| S694C |
S586 |
ND |
Maselli et al (2003) |
Alter choline-binding site |
| Residue numbers in humans are based on the 82 kDa version of ChAT. | ||||
| kcat: catalytic constant; KmAcCoA and Kmchol: Michaelis–Menten constants for the substrates acetyl coenzyme A and choline; E: expression level in COS cells (Ohno et al, 2001); ↑: increase in the value of kinetic constant; ↑↑: large increase in the value of kinetic constant; ↓: decrease in the value of kinetic constant or expression level; ND: kinetic constants and expression level not determined. | ||||