The differential ability of asparagine and glutamine in promoting the closed/active enzyme conformation rationalizes the Wolinella succinogenes L-asparaginase substrate specificity.

ABSTRACT: Many side effects of current FDA-approved L-asparaginases have been related to their secondary L-glutaminase activity. The Wolinella succinogenes L-asparaginase (WoA) has been reported to be L-glutaminase free, suggesting it would have fewer side effects. Unexpectedly, the WoA variant with a proline at position 121 (WoA-P₁₂₁) was found to have L-glutaminase activity in contrast to Uniprot entry P50286 (WoA-S₁₂₁) that has a serine residue at this position. Towards understanding how this residue impacts the L-glutaminase property, kinetic analysis was coupled with crystal structure determination of these WoA variants. WoA-S₁₂₁ was confirmed to have much lower L-glutaminase activity than WoA-P₁₂₁, yet both showed comparable L-asparaginase activity.

SUBMITTER: Nguyen HA 

PROVIDER: S-EPMC5282591 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature