Structural highlights
Publication Abstract from PubMed
Iridoid synthases belong to the family of short-chain dehydrogenase/reductase involved in the biosynthesis of iridoids. Despite having high sequence and structural homology with progesterone 5beta-reductase, these enzymes exhibit differential substrate specificities. Previously, two loops, L1 and L2 at substrate-binding pocket, were suggested to be involved in generating substrate specificity. However, the structural basis of specificity determinants was elusive. Here, combining sequence and structural analysis, site-directed mutagenesis, and molecular dynamics simulations, we have shown that iridoid synthase contains two channels for substrate entry whose geometries are altered by L1-L2 dynamics, primarily orchestrated by interactions of residues Glu161 and Gly162 of L1 and Asn358 of L2. A complex interplay of these interactions confer the substrate specificity to the enzyme.
Dynamics of loops at the substrate entry channel determine the specificity of iridoid synthases.,Sandholu AS, Mohole M, Duax WL, Thulasiram HV, Sengupta D, Kulkarni K FEBS Lett. 2018 Aug;592(15):2624-2635. doi: 10.1002/1873-3468.13174. Epub 2018, Jul 10. PMID:29944733[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Sandholu AS, Mohole M, Duax WL, Thulasiram HV, Sengupta D, Kulkarni K. Dynamics of loops at the substrate entry channel determine the specificity of iridoid synthases. FEBS Lett. 2018 Aug;592(15):2624-2635. doi: 10.1002/1873-3468.13174. Epub 2018, Jul 10. PMID:29944733 doi:http://dx.doi.org/10.1002/1873-3468.13174
