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Pregled bibliografske jedinice broj: 1104374

Substrate Channeling via a Transient Protein- Protein Complex: The case of D-Glyceraldehyde- 3-Phosphate Dehydrogenase and L-Lactate Dehydrogenase


Svedružić, Željko; Odorčić, Ivica; Chang, Christopher H.; Svedružić, Draženka
Substrate Channeling via a Transient Protein- Protein Complex: The case of D-Glyceraldehyde- 3-Phosphate Dehydrogenase and L-Lactate Dehydrogenase // Scientific reports, 10 (2020), 1; 10404-10416 doi:.org/10.1101/2020.01.22.916023 (međunarodna recenzija, članak, znanstveni)


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Naslov
Substrate Channeling via a Transient Protein- Protein Complex: The case of D-Glyceraldehyde- 3-Phosphate Dehydrogenase and L-Lactate Dehydrogenase

Autori
Svedružić, Željko ; Odorčić, Ivica ; Chang, Christopher H. ; Svedružić, Draženka

Izvornik
Scientific reports (2045-2322) 10 (2020), 1; 10404-10416

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
channeling

Sažetak
Substrate channeling studies have frequently failed to provide conclusive results due to poor understanding of this subtle phenomenon. We analyzed the mechanism of NADH-channeling from D-glyceraldehyde-3-phosphate dehydrogenase (GAPDH) to L-lactate Dehydrogenase (LDH) using enzymes from different cells. Enzyme kinetics studies showed 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 showed that LDH and GAPDH can form a leaky channeling complex only at the limiting NADH concentrations. Surface calculations showed 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. Molecular evolution or metabolic engineering protocols can exploit substrate channeling for metabolic flux control by fine- tuning substrate-binding affinity for the key enzymes in the competing reaction paths.

Izvorni jezik
Engleski



POVEZANOST RADA


Profili:

Avatar Url Željko Svedružić (autor)

Poveznice na cjeloviti tekst rada:

doi www.nature.com

Citiraj ovu publikaciju:

Svedružić, Željko; Odorčić, Ivica; Chang, Christopher H.; Svedružić, Draženka
Substrate Channeling via a Transient Protein- Protein Complex: The case of D-Glyceraldehyde- 3-Phosphate Dehydrogenase and L-Lactate Dehydrogenase // Scientific reports, 10 (2020), 1; 10404-10416 doi:.org/10.1101/2020.01.22.916023 (međunarodna recenzija, članak, znanstveni)
Svedružić, Ž., Odorčić, I., Chang, C. & Svedružić, D. (2020) Substrate Channeling via a Transient Protein- Protein Complex: The case of D-Glyceraldehyde- 3-Phosphate Dehydrogenase and L-Lactate Dehydrogenase. Scientific reports, 10 (1), 10404-10416 doi:.org/10.1101/2020.01.22.916023.
@article{article, author = {Svedru\v{z}i\'{c}, \v{Z}eljko and Odor\v{c}i\'{c}, Ivica and Chang, Christopher H. and Svedru\v{z}i\'{c}, Dra\v{z}enka}, year = {2020}, pages = {10404-10416}, DOI = {doi.org/10.1101/2020.01.22.916023}, keywords = {channeling}, journal = {Scientific reports}, doi = {doi.org/10.1101/2020.01.22.916023}, volume = {10}, number = {1}, issn = {2045-2322}, title = {Substrate Channeling via a Transient Protein- Protein Complex: The case of D-Glyceraldehyde- 3-Phosphate Dehydrogenase and L-Lactate Dehydrogenase}, keyword = {channeling} }
@article{article, author = {Svedru\v{z}i\'{c}, \v{Z}eljko and Odor\v{c}i\'{c}, Ivica and Chang, Christopher H. and Svedru\v{z}i\'{c}, Dra\v{z}enka}, year = {2020}, pages = {10404-10416}, DOI = {doi.org/10.1101/2020.01.22.916023}, keywords = {channeling}, journal = {Scientific reports}, doi = {doi.org/10.1101/2020.01.22.916023}, volume = {10}, number = {1}, issn = {2045-2322}, title = {Substrate Channeling via a Transient Protein- Protein Complex: The case of D-Glyceraldehyde- 3-Phosphate Dehydrogenase and L-Lactate Dehydrogenase}, keyword = {channeling} }

Časopis indeksira:


  • Current Contents Connect (CCC)
  • Web of Science Core Collection (WoSCC)
    • Science Citation Index Expanded (SCI-EXP)
    • SCI-EXP, SSCI i/ili A&HCI
  • Scopus
  • MEDLINE


Citati:





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