The structural basis of unique substrate recognition by Plasmodium thymidylate kinase: Molecular dynamics simulation and inhibitory studies.

ABSTRACT: Plasmodium falciparum thymidylate kinase (PfTMK) showed structural and catalytic distinctions from the host enzyme rendering it a hopeful antiprotozoal drug target. Despite the comprehensive enzymologic, structural, inhibitory and chemical synthesis approaches targeting this enzyme, the elucidation of the exact mechanism underlying the recognition of the atypical purine substrates remains to be determined. In this study, molecular dynamics (MD) simulation of a broad range of substrates and inhibitors as well as the inhibitory properties of deoxyguanosine (dG) derivatives were used to assess the PfTMK substructure molecular rearrangements. The estimated changes during the favourable binding of high affinity substrate (TMP) include lower interaction with P-loop, free residue fluctuations of

SUBMITTER: Kandeel M 

PROVIDER: S-EPMC6366710 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature