Dynamics of loops at the substrate entry channel determine the specificity of iridoid synthases
| Autor: | Durba Sengupta, Kiran Kulkarni, William L. Duax, Madhura Mohole, Hirekodathakallu V. Thulasiram, Anand S. Sandholu |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Models
Molecular 0301 basic medicine Iridoid medicine.drug_class Biophysics Dehydrogenase Molecular Dynamics Simulation Crystallography X-Ray 01 natural sciences Biochemistry Protein Structure Secondary Substrate Specificity 03 medical and health sciences chemistry.chemical_compound Biosynthesis Structural Biology Oxidoreductase Genetics medicine Iridoids Amino Acid Sequence Molecular Biology chemistry.chemical_classification Binding Sites ATP synthase biology Progesterone Reductase 010405 organic chemistry Mutagenesis Substrate (chemistry) Cell Biology 0104 chemical sciences 030104 developmental biology Enzyme chemistry Mutagenesis Site-Directed biology.protein Oxidoreductases |
| Zdroj: | FEBS Letters. 592:2624-2635 |
| ISSN: | 1873-3468 0014-5793 |
| DOI: | 10.1002/1873-3468.13174 |
| Popis: | 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 5β-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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text