BDH2 Human
Description
Biochemical Characterization
BDH2’s enzymatic activity and substrate specificity have been extensively studied. Key findings include:
Mechanistic insights:
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Stereospecific hydrogen transfer: BDH2 transfers the pro-S hydrogen from NADH to 4-oxo-L-proline, confirmed via deuterium-labeled NADH and mass spectrometry .
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pH dependence: A group with pKa ~7.3 must be deprotonated, and another with pKa ~8.7 protonated, for optimal substrate binding/catalysis .
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Thermodynamics: NADH and NAD⁺ stabilize BDH2, with ΔTₘ shifts of 8–12°C observed in differential scanning fluorimetry .
Functional Roles in Metabolism and Disease
BDH2 participates in diverse pathways:
A. 4-Oxo-L-Proline to Cis-4-Hydroxy-L-Proline
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Reaction: Reversible reduction of 4-oxo-L-proline to cis-4-hydroxy-L-proline, a non-canonical hydroxyproline isomer .
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Anticancer activity: Cis-4-hydroxy-L-proline inhibits pancreatic cancer cell growth and is under clinical evaluation .
| Cell Type | BDH2 Expression | Effect | Reference |
|---|---|---|---|
| Hepatocellular carcinoma (HCC) | Downregulated | Induces apoptosis via Bax/Bcl-2 imbalance | |
| HEK293T cells | Endogenous | Efficiently metabolizes 4-oxo-L-proline |
Iron Homeostasis and Siderophore Synthesis
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2,5-Dihydroxybenzoic acid (2,5-DHBA): BDH2 synthesizes this siderophore, critical for iron assimilation. Deficiency leads to iron overload and anemia .
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Immune regulation: Modulates iron availability during bacterial infections, affecting pathogen iron acquisition .
Clinical and Pathological Relevance
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Cancer: BDH2 downregulation in HCC correlates with poor prognosis. Overexpression induces apoptosis via caspase-3-independent pathways .
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Stem Cell Biology: Depletion in ASCs promotes endoderm differentiation, altering DNA methylation and lineage markers (e.g., Gata4, Sox17) .
Research Gaps and Future Directions
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Metabolic fate of cis-4-hydroxy-L-proline: Limited data on its cellular transport, stability, and interaction with prolyl hydroxylases.
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Therapeutic targeting: Small-molecule modulators of BDH2 activity to exploit its anticancer potential or iron-regulatory roles.
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Species-specific functions: Comparative studies in mammals vs. microbes/plants to elucidate evolutionary divergence.
Product Specs
MGSSHHHHHH SSGLVPRGSH MGRLDGKVII LTAAAQGIGQ AAALAFAREG AKVIATDINE SKLQELEKYP GIQTRVLDVT KKKQIDQFAN EVERLDVLFN VAGFVHHGTV LDCEEKDWDF SMNLNVRSMY LMIKAFLPKM LAQKSGNIIN MSSVASSVKG VVNRCVYSTT KAAVIGLTKS VAADFIQQGI RCNCVCPGTV DTPSLQERIQ ARGNPEEARN DFLKRQKTGR FATAEEIAML CVYLASDESA YVTGNPVIID GGWSL
Product Science Overview
BDH2 is a single, non-glycosylated polypeptide chain composed of 265 amino acids, with a molecular mass of approximately 28.8 kDa . The recombinant form of this enzyme is typically expressed in Escherichia coli (E. coli) and is purified using proprietary chromatographic techniques . The enzyme is often tagged with a His-tag at the N-terminus to facilitate purification .
BDH2 mediates the formation of 2,5-dihydroxybenzoic acid (2,5-DHBA), a siderophore that shares structural similarities with bacterial enterobactin . This function is crucial for iron assimilation and homeostasis, as 2,5-DHBA associates with lipocalin 2 (LCN2), playing a key role in iron metabolism . Additionally, BDH2 acts as a 3-hydroxybutyrate dehydrogenase, converting 3-hydroxybutyrate into acetoacetate, which is an essential step in ketone body metabolism .
The recombinant form of BDH2 is used extensively in biochemical research to study its role in ketone body metabolism and iron homeostasis . It is also utilized in high-throughput screening assays and other experimental setups to understand its enzymatic properties and potential therapeutic applications .
