The pyridoxal phosphate-binding protein (PLPBP) family (also termed ProsC/PROSC or COG0325 family) members are found in all kingdoms of life, exemplified by the proteins YBL036C (yeast), YggS (Gram-negative bacteria), YlmE (Gram-positive bacteria), PipY (cyanobacteria), PLPHP (humans) and HTH5 (rice).
Organism | Protein | PDB File | Vitamer | Ligands | Amino Acid Changes | Resolut. (Å) |
Deposition Year | Ref. | ||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Escherichia coli | YggS | 1W8G | PLP | Isocitrate | None | 2.00 | 2004 | – | ||||||||
3SY1 | PLP | MES Acetate |
L32V/G56S/N58H/H81N/ I83A/H102I/M165S/S202A/ M205Q/R221A hexamutant |
1.47 | 2011 | – | ||||||||||
7UBQ | PNP * | None | None | 2.60 | 2022 | – | ||||||||||
7UB4 | PLP | None | K36A/K38A/K233A/K234 | 2.40 | 2022 | – | ||||||||||
7UAX | None | PO4H3 | K36A/K38A | 2.07 | 2022 | – | ||||||||||
7U9H | None | SO4H2 | None | 2.00 | 2022 | – | ||||||||||
7UBP | PLP | SO4H2 | K36A/K137A | 2.30 | 2022 | – | ||||||||||
7UB8 | PLP | Butanediol | K38A/K137A/K233A/K234A | 2.30 | 2022 | – | ||||||||||
7UAU | PLP | SO4H2 | K137A | 2.10 | 2022 | – | ||||||||||
7UAT | PLP | PO4H3 | K36A | 2.00 | 2022 | – | ||||||||||
7U9C | PLP | PO4H3 | None | 2.10 | 2022 | – | ||||||||||
Bifidobacterium adolescentis |
YggS | 3CPG | PLP | Acetate | Se-Met ** | 1.71 | 2008 | |||||||||
T116 | 7 | T116I | Seizures | – | ||||||||||||
Severe disease | 2 | [ | 43 | ][39] | 2 (1 homozygous; 1 homozygous (T116I/H275D)) |
Proposed ↓ in PLP saturation | Structural modeling of HuPLPHP | [43][39] | Agrobacterium tumefaciens | YggS | ||||||
L175 | 6 | 3R79 | PLP | L175P | Seizures Severe disease 2Acetate Pr+3 |
[Se-Met ** | 1.90 | 2011 | 41– | |||||||
] | 1 (homozygous) | Misfolding | In vitro studies on rHuPLPHP | [ | 23 | ] | Synechococcus elongatus | PipY | 5NLC | None | PO4H3 | |||||
R205 | 7 | R205Q | None | 1.90 | 2017 | [ | 22 | ] | ||||||||
Seizures | Moderate disease | 2 | [44][36] [54][38] |
1 (R205Q/null) 1 (homozygous) |
↓thermostability | In vitro studies on rHuPLPHP | [23] | 5NM8 | PLP | Ca2+ | None | 1.93 | 2017 | [22] | ||
Fusobacterium nucleatum | YggS | 7F8E | None | SO4H2 | Se-Met ** | 2.08 | 2021 | – | ||||||||
6KZW | None | PO4H3 | T5A/N202S, Se-Met ** | 2.08 | 2019 | – | ||||||||||
7YGF | Structure not released | 2.08 | 2022 | [24] | ||||||||||||
Saccharomyces cerevisiae | YBL036C | 1CT5 | PLP | None | Se-Met ** | 2.00 | 1999 | [21] | ||||||||
1B54 | PLP | None | None | 2.10 | 1999 | [21] |
Amino Acid Change in HuPLPHP | Molecular Mechanism: Effect on PLPBP Protein | |||||||
---|---|---|---|---|---|---|---|---|
Amino acid | Conserv. Score 1 | Change | Clinical effects | Reported in | Number of patients | Observed effect | Inferred from | Ref. |
P40 | 7 | P40L | Seizures | [44][36] [51][37] |
1 (P40L/R241Q) 1 (P40L/splicing) |
↓ thermostability | In vitro studies on rHuPLPHP | [23] |
R41 | 4 | R41Q | Seizures Mild disease 2 |
[54][38] [43][39] |
2 (homozygous;R41Q/V45D) 3 (homozygous) |
↓yield/misfolding? ↓thermostability |
In vitro studies on rHuPLPHP | [36][35] |
R41W | Seizures, death | [50][40] | 1 (homozygous) | NT | NT | NT | ||
V45 | 9 | V45D | Seizures | [54][38] | 1 (R41Q/V45D) | ↓↓PLP content ↓ thermostability |
In vitro studies on rHuPLPHP | [36][35] |
K47 | 9 | K47A | Not reported in humans (prenatally lethal?) | lack of PLP | rEcyggSK36A | [31][30] | ||
E67 | 9 | E67K | Seizures Severe disease 2 |
[54][38] [43][39] |
1 (homozygous) 3 (homozygous) |
Misfolding | In vitro studies on rHuPLPHP | [36][35] |
Y69 | 7 | Y69C | Seizures Moderate disease 2 |
[44][36] | 1 (homozygous) | Higher dimerization ↓PLP content |
In vitro studies on rHuPLPHP | [23] |
P87 | 1 | P87L | Seizures Severe disease 2 |
[41] [44][36] [53][42] |
1(P87L/R241Q) 1 (homozygous) 1 (P87L/splicing) |
↓solubility/misfolding | In vitro studies on rHuPLPHP | [23] |
I94 | 8 | I94F | Seizures Mild disease 2 |
[43][39] | 1 (homozygous) | Proposed ↓ in PLP saturation | Structural modeling of HuPLPHP | [43][39] |
M113 | 6 | M113T | Seizures | [51][37] | 1 (M113T/C15X) | NT | NT | NT |
G224 | ||||||||
9 | G224A | Seizures | Severe disease 2 |
[43][39] | 1 (G224A/splicing) | Proposed ↓ in PLP saturation | Structural modeling of HuPLPHP | [43][39] |
S226 | 9 | S226A | Not reported in humans (prenatally lethal?) | ↓PLP saturation | rFnS201A | [24] | ||
R241 | 9 | R241Q | Seizures | [41] [44][36] [52][43] |
1 (P87L/R241Q) 1 (P40L/R241Q) 1(R241Q/splicing) |
↓solubility ↓thermostability ↓PLP binding |
In vitro studies on rHuPLPHP In vitro studies on rSePipYR210Q |
[22,23][22][23] |
I242 | 7 | I242T | Seizures | [45][44] | 1 (homozygous) | NT | NT | NT |
H275 | NA | H275D | Seizures | [43][39] | 1 (homozygous T116I/H275D) | Variant of uncertain significance (VUS) | Structural modeling of HuPLPHP | [43][39] |