Application | Comment | Organism |
---|---|---|
medicine | A140P is a naturally occuring mutation in patients with pulmonary hypertrophic osteoarthropathy. Homozygous individuals develop pulmonary hypertrophic osteoarthropathy secondary to chronically elevated prostaglandin E2 levels. Heterozygous relatives also show milder biochemical and clinical manifestations. Identification of an insertion-deletion mutation in 15-hydroxyprostaglandin dehydrogenase exon 3, this alters the open reading frame from codon 78, truncating the protein after ten altered amino acids, and of a homozygous 2-bp deletion within the duplicated dinucleotide CTCT at nucleotides 175 and 176. This alters the reading frame from residue 59 and truncates the HPGD protein at residue 65 after seven altered amino acids. Both of these predicted truncated proteins lack the entire PGE2-binding domain and cause primary hypertrophic osteoarthropathy | Homo sapiens |
Cloned (Comment) | Organism |
---|---|
expressed in Escherichia coli strain JM109(DE3) | Homo sapiens |
expression in Escherichia coli | Homo sapiens |
Crystallization (Comment) | Organism |
---|---|
modeling of structure for mutant A140P. Mutation disrupts binding of the substrate prostaglandin E2 both because the pyrrolidine ring of Pro140 fills a space that in the wildtype complex is occupied by the prostaglandin E2 target side-chain 15-OH and because there is a resulting loss of catalytically important hydrogen bonding of the 15-OH to the nearby serine at residue 138 | Homo sapiens |
Protein Variants | Comment | Organism |
---|---|---|
A140P | naturally occuring mutation in patients with pulmonary hypertropic osteoarthropathy. Homozygous individuals develop pulmonary hypertrophic osteoarthropathy secondary to chronically elevated prostaglandin E2 levels. Heterozygous relatives also show milder biochemical and clinical manifestations. After expression in Escherichia coli, the mutations renders the protein largely insoluble at 37°C, but mostly souble at 20°C. Mutant exhibits less than 1.5% of wild-type activity | Homo sapiens |
A140P | the mutant shows no detectable activity, the A140P substitution renders the enzyme largely insoluble at 37°C, at 27°C, the mutant protein is partially soluble, and at 20°C it is mostly soluble | Homo sapiens |
additional information | identification of an insertion-deletion mutation in 15-hydroxyprostaglandin dehydrogenase exon 3, this alters the open reading frame from codon 78, truncating the protein after ten altered amino acids, and of a homozygous 2-bp deletion within the duplicated dinucleotide CTCT at nucleotides 175 and 176. This alters the reading frame from residue 59 and truncates the HPGD protein at residue 65 after seven altered amino acids. Both of these predicted truncated proteins lack the entire PGE2-binding domain and cause primary hypertrophic asteoarthropathy | Homo sapiens |
General Stability | Organism |
---|---|
the assay mix containing 50 mM Tris HCl, pH 7.5, 1 mM dithiothreitol, 100 mM prostaglandin E2 and 1 mM NAD+ at 22°C is not optimal for HPGD activity, but avoids a sharp, unphysiological pH optimum around pH 9 | Homo sapiens |
Molecular Weight [Da] | Molecular Weight Maximum [Da] | Comment | Organism |
---|---|---|---|
31000 | - |
wild type recombinant protein, SDS-PAGE | Homo sapiens |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | - |
- |
- |
Homo sapiens | - |
patients with primary hypertrophic osteoarthropathy | - |
Purification (Comment) | Organism |
---|---|
nickel-Sepharose column chromatography | Homo sapiens |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
prostaglandin E2 + NAD+ | the wild type enzyme is highly active against prostaglandin E2 and NAD+ | Homo sapiens | 15-ketoprostaglandin E2 + NADH + H+ | - |
? |
Synonyms | Comment | Organism |
---|---|---|
15-hydroxyprostaglandin dehydrogenase | - |
Homo sapiens |
HPGD | - |
Homo sapiens |
NAD+-dependent 15-hydroxyprostaglandin dehydrogenase | - |
Homo sapiens |
Temperature Stability Minimum [°C] | Temperature Stability Maximum [°C] | Comment | Organism |
---|---|---|---|
37 | - |
when expression is induced at 37°C, almost all wild type recombinant HPGD protein is soluble | Homo sapiens |
Cofactor | Comment | Organism | Structure |
---|---|---|---|
NAD+ | dependent on | Homo sapiens |