| Title : Identical active sites in hydroxynitrile lyases show opposite enantioselectivity and reveal possible ancestral mechanism - Jones_2017_ACS.Catal_7_4221 |
| Author(s) : Jones BJ , Bata Z , Kazlauskas RJ |
| Ref : ACS Catal , 7 :4221 , 2017 |
| Abstract : Evolutionarily related hydroxynitrile lyases from rubber tree (HbHNL) and from Arabidopsis thaliana (AtHNL) follow different catalytic mechanisms with opposite enantioselectivity toward mandelonitrile. We hypothesized that the HbHNL-like mechanism evolved from an enzyme with an AtHNL-like mechanism. We created ancestor-like composite active-sites in each scaffold to elucidate how this transition may have occurred. Surprisingly, a composite active site in HbHNL maintained (S)-selectivity, while the identical set of active site residues in AtHNL maintained (R)-selectivity. Composite active-site mutants that are (S)-selective without the Lys236 and Thr11 that are required for the classical (S)-HNL mechanism suggests a new mechanism. Modeling suggested a possibility for this new mechanism that does not exist in modern enzymes. Thus, the last common ancestor of HbHNL and AtHNL may have used an extinct mechanism, not the AtHNL-like mechanism. Multiple mechanisms are possible with the same catalytic residues and residues outside the active site strongly influence mechanism and enantioselectivity. |
| ESTHER : Jones_2017_ACS.Catal_7_4221 |
| PubMedSearch : Jones_2017_ACS.Catal_7_4221 |
| PubMedID: 28798888 |
| Gene_locus related to this paper: arath-HNL , hevbr-hnl |
Jones BJ, Bata Z, Kazlauskas RJ (2017)
Identical active sites in hydroxynitrile lyases show opposite enantioselectivity and reveal possible ancestral mechanism
ACS Catal
7 :4221
Jones BJ, Bata Z, Kazlauskas RJ (2017)
ACS Catal
7 :4221