Structural highlights
Publication Abstract from PubMed
Dehydroascorbate reductase (DHAR), a member of the glutathione-S-transferase (GST) family, reduces dehydroascorbate (DHA) to ascorbate (AsA; Vitamin-C) in a glutathione (GSH)-dependent manner and in doing so, replenishes the critical AsA pool of the cell. To understand the enzyme mechanism in detail, we determined the crystal structure of a plant DHAR from Pennisetum glaucum (PgDHAR) using Iodide-Single Anomalous Dispersion (SAD) and Molecular replacement methods, in two different space groups. Here, we show PgDHAR in complex with two non-native ligands, viz. an acetate bound at the G-site, which resembles the gamma-carboxyl moiety of GSH, and a glycerol at the H-site, which shares the backbone of AsA. We also show that, in the absence of bound native substrates, these non-native ligands help define the critical 'hook points' in the DHAR enzyme active site. Further, our data suggest that these non-native ligands can act as the logical bootstrapping points for iterative design of inhibitors/analogs for DHARs.
Non-native ligands define the active site of Pennisetum glaucum (L.) R. Br dehydroascorbate reductase.,Krishna Das B, Kumar A, Maindola P, Mahanty S, Jain SK, Reddy MK, Arockiasamy A Biochem Biophys Res Commun. 2016 May 13;473(4):1152-7. doi:, 10.1016/j.bbrc.2016.04.031. Epub 2016 Apr 9. PMID:27067046[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Krishna Das B, Kumar A, Maindola P, Mahanty S, Jain SK, Reddy MK, Arockiasamy A. Non-native ligands define the active site of Pennisetum glaucum (L.) R. Br dehydroascorbate reductase. Biochem Biophys Res Commun. 2016 May 13;473(4):1152-7. doi:, 10.1016/j.bbrc.2016.04.031. Epub 2016 Apr 9. PMID:27067046 doi:https://dx.doi.org/10.1016/j.bbrc.2016.04.031
