Babkova_2020_Comput.Struct.Biotechnol.J_18_1497

Reference

Title : Structures of hyperstable ancestral haloalkane dehalogenases show restricted conformational dynamics - Babkova_2020_Comput.Struct.Biotechnol.J_18_1497
Author(s) : Babkova P , Dunajova Z , Chaloupkova R , Damborsky J , Bednar D , Marek M
Ref : Comput Struct Biotechnol J , 18 :1497 , 2020
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 (DeltaT (m) up to 24 degreeC), 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.

PubMedSearch : Babkova_2020_Comput.Struct.Biotechnol.J_18_1497
PubMedID: 32637047
Gene_locus related to this paper: 9bact-AncHLD3 , 9bact-AncHLD2 , 9bact-AncHLD5

Related information

Gene_locus 9bact-AncHLD3    9bact-AncHLD2    9bact-AncHLD5
Structure 9bact-AncHLD3    9bact-AncHLD2    9bact-AncHLD5    6Y9E    6Y9F    6Y9G

Citations formats

Babkova P, Dunajova Z, Chaloupkova R, Damborsky J, Bednar D, Marek M (2020)
Structures of hyperstable ancestral haloalkane dehalogenases show restricted conformational dynamics
Comput Struct Biotechnol J 18 :1497

Babkova P, Dunajova Z, Chaloupkova R, Damborsky J, Bednar D, Marek M (2020)
Comput Struct Biotechnol J 18 :1497