Table 1. Structural analysis of HIBM-associated missense mutations in the GNE kinase domain.
Missense Mutationa | Epimerase Activity (%)b | Kinase Activity (%)b | Oligomeric Statec | Relative Accessibility in monomerd | Relative Accessibility in dimerd | Secondary structure elemente | Mutation site feature | Mutation group |
V421A | 0.007 | 0.007 | β-strand | Buried | IV | |||
A460V | 0.018 | 0.018 | Helix | Buried | IV | |||
I472T | 50 | 5 | 0.000 | 0.000 | β-strand | Buried | IV | |
P511H | 0.416 | 0.416 | Loop | Exposed | III | |||
P511L | 0.416 | 0.416 | Loop | Exposed | III | |||
N519S | 40 | 20 | hexameric | 0.027 | 0.027 | Helix | Interlobar | II |
A524V | 5 | 50 | 0.000 | 0.000 | Helix | Interlobar | II | |
F528C | 70 | 35 | hexameric | 0.140 | 0.140 | helix end | Interlobar | II |
F537I | 45 | 60 | 0.000 | 0.000 | β-strand start | Buried | IV | |
I557T | 0.297 | 0.005 | Loop | Dimer | I | |||
G559R | 0.470 | 0.229 | Loop | Dimer | I | |||
V572L | 70 | 10 | 0.221 | 0.000 | Loop | Dimer | I | |
G576E | 15 | 15 | trimeric | 0.254 | 0.254 | Loop | Dimer | I |
I587T | 55 | 35 | 0.000 | 0.000 | helix start | Buried | IV | |
A591T | 0.009 | 0.009 | Helix | Buried | IV | |||
A600T | 0.000 | 0.000 | Helix | Buried | IV | |||
A630T | 80 | 40 | 0.000 | 0.000 | Helix | Buried | IV | |
A631T | 80 | 75 | hexameric | 0.109 | 0.109 | Helix | Buried | IV |
A631V | 70 | 65 | hexameric | 0.109 | 0.109 | Helix | Buried | IV |
I656N | 0.038 | 0.005 | Helix | Buried | IV | |||
Y675H | 0.000 | 0.000 | Helix | Buried | IV | |||
V679G | 0.000 | 0.000 | Helix | Buried | IV | |||
V696M | 0.020 | 0.020 | β-strand | Buried | IV | |||
G708S | 45 | 5 | 0.000 | 0.000 | β-strand | Interlobar | II | |
M712T | 100 | 70 | 0.155 | 0.155 | Helix | Interlobar | II |
UDP-GlcNAc epimerase and ManNAc kinase activities are percentage values relative to the corresponding activities of the full length wild type GNE. Data extracted from reference [11].
Oligomeric state of the full length mutant GNE. Data extracted from reference [11].
Relative solvent accessibility of the residue calculated using the DSSP program [30] and normalized according to values in reference [31]. A value of 1 means full exposure of the residue while a value of 0 means the residue is fully buried.
The type of the secondary structure element the residue is located at was assigned using the DSSP program [30].