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Literature summary for 1.2.1.12 extracted from

  • Svedruzic, Z.M.; Odorcic, I.; Chang, C.H.; Svedruzic, D.
    Substrate channeling via a transient protein-protein complex The case of D-glyceraldehyde-3-phosphate dehydrogenase and L-lactate dehydrogenase (2020), Sci. Rep., 10, 10404 .
    View publication on PubMedView publication on EuropePMC

Application

Application Comment Organism
biotechnology molecular evolution or metabolic engineering protocols can exploit substrate channeling of D-glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and L-lactate dehydrogenase (LDH) for metabolic flux control by fine-tuning substrate-binding affinity for the key enzymes in the competing reaction paths Oryctolagus cuniculus

Localization

Localization Comment Organism GeneOntology No. Textmining
cytosol
-
Oryctolagus cuniculus 5829
-

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
D-glyceraldehyde 3-phosphate + phosphate + NAD+ Oryctolagus cuniculus
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3-phospho-D-glyceroyl phosphate + NADH + H+
-
?

Organism

Organism UniProt Comment Textmining
Oryctolagus cuniculus P46406
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-

Source Tissue

Source Tissue Comment Organism Textmining
skeletal muscle
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Oryctolagus cuniculus
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Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
D-glyceraldehyde 3-phosphate + phosphate + NAD+
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Oryctolagus cuniculus 3-phospho-D-glyceroyl phosphate + NADH + H+
-
?

Subunits

Subunits Comment Organism
homotetramer
-
Oryctolagus cuniculus

Synonyms

Synonyms Comment Organism
D-glyceraldehyde-3-phosphate dehydrogenase
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Oryctolagus cuniculus
GAPDH
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Oryctolagus cuniculus
rmGAPDH
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Oryctolagus cuniculus

Cofactor

Cofactor Comment Organism Structure
NAD+
-
Oryctolagus cuniculus

General Information

General Information Comment Organism
metabolism mechanism of NADH-channeling from D-glyceraldehyde-3-phosphate dehydrogenase (GAPDH) to L-lactate dehydrogenase (LDH). Enzyme kinetics studies show that LDH activity with free NADH and GAPDH-NADH complex always take place in parallel. The channeling is observed only in assays that mimic cytosolic conditions where free NADH concentration is negligible and the GAPDH-NADH complex is dominant. Molecular dynamics and protein-protein interaction studies show that LDH and GAPDH can form a leaky channeling complex only at the limiting NADH concentrations. Surface calculations show that positive electric field between the NAD(H) binding sites on LDH and GAPDH tetramers can merge in the LDH-GAPDH complex. NAD(H)-channeling within the LDH-GAPDH complex can be an extension of NAD(H)-channeling within each tetramer. In the case of a transient LDH-(GAPDH-NADH) complex, the relative contribution from the channeled and the diffusive paths depends on the overlap between the off-rates for the LDH-(GAPDH-NADH) complex and the GAPDH-NADH complex. The GAPDH complex can be observed in cell extracts, and with purified proteins in conditions that mimic high protein concentrations in cytosol Oryctolagus cuniculus
additional information docking and molecular dynamics simulations of the interaction between rabbit muscle GAPDH and rabbit muscle or porcine heart LDH, structure analysis and calculation of the rm(ph)LDH-rmGAPDH complex, overview. Multiscale MD calculations and molecular docking studies showed that rmLDH and rmGAPDH can form a dynamic complex facing each other with their NAD(H) binding sites. The complex breaks apart when the two enzymes are saturated with NAD(H) molecules. The complex breaks apart when the two enzymes are saturated with NAD(H) molecules. When rmLDH and rmGAPDH form a complex, the positive cavities on the surface of each enzyme merge to form a central positive cavity under the protein surface. The cavity connects four NAD(H) binding sites with an average separation of 2.9 nm between the adjacent sites. Thus, NADH channeling within the rmLDH-rmGAPDH complex can be an extension of NADH channeling between the two adjacent monomers in rmLDH and rmGAPDH tetramers. Analysis of interaction between phLDH and byGAPDH by analytical ultracentrifugation, on velocity experiments for detection of interaction between phLDH and byGAPDH. It is a transient protein-protein interactions and NADH channeling in cells Oryctolagus cuniculus