6Y9F
Crystal structure of putative ancestral haloalkane dehalogenase AncHLD3 (node 3)
Summary for 6Y9F
| Entry DOI | 10.2210/pdb6y9f/pdb |
| Descriptor | Ancestral haloalkane dehalogenase AncHLD3, 2-[N-CYCLOHEXYLAMINO]ETHANE SULFONIC ACID (3 entities in total) |
| Functional Keywords | haloalkane dehalogenase, hydrolase |
| Biological source | synthetic construct |
| Total number of polymer chains | 1 |
| Total formula weight | 34488.44 |
| Authors | Chaloupkova, R.,Damborsky, J.,Marek, M. (deposition date: 2020-03-09, release date: 2020-11-18, Last modification date: 2024-01-24) |
| Primary citation | Babkova, P.,Dunajova, Z.,Chaloupkova, R.,Damborsky, J.,Bednar, D.,Marek, M. Structures of hyperstable ancestral haloalkane dehalogenases show restricted conformational dynamics. Comput Struct Biotechnol J, 18:1497-1508, 2020 Cited by PubMed Abstract: Ancestral sequence reconstruction is a powerful method for inferring ancestors of modern enzymes and for studying structure-function relationships of enzymes. We have previously applied this approach to haloalkane dehalogenases (HLDs) from the subfamily HLD-II and obtained thermodynamically highly stabilized enzymes (Δ up to 24 °C), showing improved catalytic properties. Here we combined crystallographic structural analysis and computational molecular dynamics simulations to gain insight into the mechanisms by which ancestral HLDs became more robust enzymes with novel catalytic properties. Reconstructed ancestors exhibited similar structure topology as their descendants with the exception of a few loop deviations. Strikingly, molecular dynamics simulations revealed restricted conformational dynamics of ancestral enzymes, which prefer a single state, in contrast to modern enzymes adopting two different conformational states. The restricted dynamics can potentially be linked to their exceptional stabilization. The study provides molecular insights into protein stabilization due to ancestral sequence reconstruction, which is becoming a widely used approach for obtaining robust protein catalysts. PubMed: 32637047DOI: 10.1016/j.csbj.2020.06.021 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.26 Å) |
Structure validation
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