The E. coli L‐asparaginase V27T mutant: structural and functional characterization and comparison with theoretical predictions
- Center for Structural Biology, Center for Cancer Research National Cancer Institute Frederick MD USA
Bacterial L‐asparaginases have been used for over 40 years as anticancer drugs. Ardalan et al. (Medical Hypotheses112, 7–17, 2018) proposed that the V27T mutant ofEscherichia colitype II L‐asparaginase, EcAII(V27T), should display altered biophysical and catalytic properties compared to the wild‐type enzyme, EcAII(wt), rendering it more favourable as a pharmaceutical. They postulated that EcAII(V27T) would exhibit reduced glutaminolytic activity and be more stable compared to EcAII(wt). Their postulates, however, were purely theoretical. Here, we characterized experimentally selected properties of EcAII(V27T). We found asparaginolytic activity of this mutant unchanged, whereas its glutaminolytic activity was fourfold lower compared with EcAII(wt). We did not observe significant differences in stabilities of EcAII(wt) and EcAII(V27T). Crystal structures of the complexes with L‐Asp and L‐Glu showed considerable differences in binding modes of both substrates.
- Research Organization:
- Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
- Sponsoring Organization:
- USDOE
- DOE Contract Number:
- AC02-06CH11357
- OSTI ID:
- 2423690
- Journal Information:
- FEBS Letters, Journal Name: FEBS Letters Journal Issue: 23 Vol. 596; ISSN 0014-5793
- Publisher:
- Federation of European Biochemical Societies
- Country of Publication:
- United States
- Language:
- English
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