Structural characterization of the reported missense mutations in URO-D
| Residue change . | Structural location . | Probable effect of mutation . |
|---|---|---|
| G25E | H1-S2 | Tight turn, restricted main chain |
| P62L | HC-H1 | Residue within disordered loop, unknown function or effect of mutation |
| A80S/G | S2 | No explanation |
| V134Q | H2 | Polar residue into a hydrophobic pocket |
| R144P | H2 | Salt bridge between R144 and Q63, helix-helix stability; P is also a helix breaker |
| G156D | S3-HG | Tight turn and restricted side-chain access |
| M165R | HG | Charged residue inserted into a hydrophobic pocket |
| E167K4-151 | HG | Charge reversal and the E167 links residues in a surface loop |
| G168R | HG-HH | Tight turn, restricted main chain |
| R193P | H3 | Pro insertion into middle of helix |
| L195F | H3 | No explanation |
| L216Q | S4 | Hydrophilic residue placed into hydrophobic core, near active site |
| E218K | S4 | Charge reversal and longer side chain, near active site |
| H220P4-151 | S4-HI | Histidine links residues in the intersection of several loops, proline is rigid and hydrophobic |
| F229L4-151 | H4 | No explanation |
| F232L4-151 | H4 | No explanation |
| L253Q | H4-S5 | No explanation |
| I260T | S5 | No explanation, water molecule replaces extra carbon atom |
| G281E/V | S6 | Mutant side chain protrudes into active site cleft |
| L282R4-151 | S6 | Charged residue inserted into a hydrophobic pocket, near active site |
| R292G4-151 | H6 | Arginine forms a salt bridge between H6 and S8 |
| G303S | S7 | Gly in conformationally strained conformation, side-chain conflicts |
| N304K4-151 | S2 | Tightly packed between H6 and H7, no room for longer Lys side chain |
| Y311C4-150 | HJ | Tyrosine packs against Arg179 side chain not supported by Cys, at dimer interface |
| G318R4-151 | H7 | Glycine lies on an internal turn of helix, large side chains disrupt packing |
| M324T4-151 | H7 | Side chain points toward protein disrupts packing of helix, dimer interface |
| R332H | S8 | No explanation |
| I334T | S8 | No explanation |
| Residue change . | Structural location . | Probable effect of mutation . |
|---|---|---|
| G25E | H1-S2 | Tight turn, restricted main chain |
| P62L | HC-H1 | Residue within disordered loop, unknown function or effect of mutation |
| A80S/G | S2 | No explanation |
| V134Q | H2 | Polar residue into a hydrophobic pocket |
| R144P | H2 | Salt bridge between R144 and Q63, helix-helix stability; P is also a helix breaker |
| G156D | S3-HG | Tight turn and restricted side-chain access |
| M165R | HG | Charged residue inserted into a hydrophobic pocket |
| E167K4-151 | HG | Charge reversal and the E167 links residues in a surface loop |
| G168R | HG-HH | Tight turn, restricted main chain |
| R193P | H3 | Pro insertion into middle of helix |
| L195F | H3 | No explanation |
| L216Q | S4 | Hydrophilic residue placed into hydrophobic core, near active site |
| E218K | S4 | Charge reversal and longer side chain, near active site |
| H220P4-151 | S4-HI | Histidine links residues in the intersection of several loops, proline is rigid and hydrophobic |
| F229L4-151 | H4 | No explanation |
| F232L4-151 | H4 | No explanation |
| L253Q | H4-S5 | No explanation |
| I260T | S5 | No explanation, water molecule replaces extra carbon atom |
| G281E/V | S6 | Mutant side chain protrudes into active site cleft |
| L282R4-151 | S6 | Charged residue inserted into a hydrophobic pocket, near active site |
| R292G4-151 | H6 | Arginine forms a salt bridge between H6 and S8 |
| G303S | S7 | Gly in conformationally strained conformation, side-chain conflicts |
| N304K4-151 | S2 | Tightly packed between H6 and H7, no room for longer Lys side chain |
| Y311C4-150 | HJ | Tyrosine packs against Arg179 side chain not supported by Cys, at dimer interface |
| G318R4-151 | H7 | Glycine lies on an internal turn of helix, large side chains disrupt packing |
| M324T4-151 | H7 | Side chain points toward protein disrupts packing of helix, dimer interface |
| R332H | S8 | No explanation |
| I334T | S8 | No explanation |