VDR: Mutation & Modification Data / (13-Oct-99)
| A. Mutations in the LBD. | ||
|---|---|---|
| This table lists all mutations known from the literature or from informal communication
up to the date given above. Complete citations are given in the Bibliography. Highlighting indicates mutations
deemed most relevant to 1,25-(OH)2-D3 binding.
| ||
| Change | Effect | Reference |
| C190W* | familial VDRR-II | Thompson et al. (1991) |
| S225A | Kd for ligand unchanged | Väisänen et al. (1998) |
| H229A | Kd for ligand increased by 27X | Väisänen et al. (1998) |
| D232A | Kd for ligand increased by 30X | Väisänen et al. (1998) |
| L233? | ||
| V234A | Kd for ligand almost unchanged | Väisänen et al. (1998) |
| S235A | Kd for ligand almost unchanged | Väisänen et al. (1998) |
| Y236A | Kd for ligand increased by 3.5X | Väisänen et al. (1998) |
| S237A | Kd for ligand increased by 27X | Väisänen et al. (1998) |
| K240A | Kd for ligand almost unchanged | Väisänen et al. (1998) |
| I242A | Kd for ligand almost unchanged | Väisänen et al. (1998) |
| F244G | impaired transactivation | Whitfield et al. (1995) |
| K246A | Kd for ligand increased by 2X | Väisänen et al. (1998) |
| K246R | ||
| L254G | impaired transactivation; no RXR heterodimer formed | Whitfield et al. (1995) |
| Q259P | dimerization (w/ RXR) inhibited | |
| R274L* | ligand binding severely decreased; VDRR-II | Kristjansson et al. (1993) |
| S275A | Kd for ligand increased by 5.3X | Väisänen et al. (1998) |
| M284A | ligand binding 50% of WT (unpublished) | Ray, Swamy (1999) |
| M284S | ligand binding 60% of WT | |
| W286A | no ligand binding (unpublished) | Ray, Swamy (1999) |
| W286F | no ligand binding | |
| C288G | ligand binding "attenuated severely" at 37 ° C; decreased 3X at 4 ° C; VDRR-II | Nakajima et al. (1996) |
| Y295STOP* | no ligand binding | Ritchie et al. (1989) |
| H305Q* | ligand binding decreased 5X | Malloy et al. (1997) |
| I314S* | reduced transactivation; high ligand conc. restores it; RXR interaction diminished | Whitfield et al. (1996) |
| C337G | ligand binding moderately decreased at 37 ° C | Nakajima et al. (1996) |
| C369G | ligand binding only mildly affected at 37 ° C | Nakajima et al. (1996) |
| K386Q | very slight decrease in ligand binding | Masuyama et al. (1997) |
| L387STOP | no ligand binding detectable | Masuyama et al. (1997) |
| R391C* | transactivation decreased together with RXR binding | Whitfield et al. (1996) |
| H397? | ||
| L404STOP | Kd for ligand increased by 10X | Masuyama et al. (1997) |
| L417A | no change in ligand binding; transcriptional activation gone | Jurutka et al. (1997) |
| L417S | ligand binding normal; transactivation abolished (also coactivator binding) | Masuyama et al. (1997) |
| V418 | contacts ligand? | |
| E420A | no change in ligand binding; transcriptional activation gone | Jurutka et al. (1997) |
| E420Q | ligand binding normal; transactivation abolished (also coactivator binding) | Masuyama et al. (1997) |
| F422 | contacts ligand? | |
| E425Q | no effect on ligand binding or transactivation | Masuyama et al. (1997) |
| B. Mutations in the DBD | ||
| Change | Effect | Reference |
| G33D H35Q K45E G46D F47I R50Q R73Q R80Q |
||
| C. Modifications | ||
|
1. Proteolysis 2. Affinity labeling 3. Photoaffinity labeling | ||
3-bromoacetyl-1,25-(OH)2-D3
Other modifications?
Site-directed mutants
Created in the Ray laboratory
From literature
Sean Quinlan <wwwadmin@darwin.bu.edu> last modified: Saturday, October 30, 1999 11:04:54 AM