Home
This Title All WIREs
WIREs RSS Feed
How to cite this WIREs title:
WIREs Comput Mol Sci
Impact Factor: 8.836

Rationalization of stereoselectivity in enzyme reactions

Full article on Wiley Online Library:   HTML PDF

Can't access this content? Tell your librarian.

Enzymes are responsible for more than 5,000 different types of biochemical reactions. Enzymes speed up various chemical reactions in cell that would otherwise take millions of years to occur in milliseconds. The ability to discriminate between optical isomers is vital for living systems. The selective formation of only one product stereoisomer from achiral substrates is one of the most sophisticated tasks for enzymes. Because of the importance of stereoselectivity in biology, the structural and mechanistic basis underlying these phenomena has become the subject of intensive research. Enzymatic reactions provide the basis of cellular biochemistry and typically display high stereoselectivity. With the advances of enzyme engineering, in vitro evolution and, especially, computational rational design, scientists start to provide various methods and tools to manipulate the stereoselective properties of enzymes. To gain an insightful view of stereoselectivity in enzyme reactions, we present an extensive discussion on the latest progresses in this area.

This article is categorized under:

  • Structure and Mechanism > Computational Biochemistry and Biophysics
  • Structure and Mechanism > Reaction Mechanisms and Catalysis
  • Molecular and Statistical Mechanics > Molecular Dynamics and Monte‐Carlo Methods
Scheme of enzyme catalysis. (a) The catalytic process and induced fit effect of enzyme. (b) The activation energy of enzyme catalysis compared to that of no enzyme reactions
[ Normal View | Magnified View ]
Calculated activation energy barrier and substrate−water distances of LEH variant SZ719. (a) The catalysis scheme of LEH. (b) The activation energy barrier of SZ719–CYO1. Distance in blue was calculated by QM methods. (c) Distances of C1O2 and C2O2 along MD simulations of SZ719–CYO1. (d) The activation energy barrier of SZ719–CYO3. Distance in blue was calculated by QM methods. (e) Distances of C1O2 and C2O2 along MD simulations of SZ719–CYO3. (Reprinted with permission from Reference . Copyright 2018 American Chemical Society)
[ Normal View | Magnified View ]
Two dominant binding modes of fluoroacetate dehalogenases (FAcD) substrates and their relative ligand binding energies. (a) The reaction scheme of FAcD. (b) The binding mode 1 of (S)‐1, with ΔGS1 = −60.1 ± 1.1 kcal/mol (−35.4 ± 0.7, monomer). (c) The binding mode 2 of (S)‐1, with ΔGS2 = −28.1 ± 0.4 kcal/mol (−14.4 ± 0.9, monomer). (d) The binding mode 1 of (R)‐1, with ΔGR1 = −35.7 ± 0.7 kcal/mol (−16.4 ± 0.8, monomer). (e) The binding mode 2 of (R)‐1, with ΔGS2 = −17.5 ± 1.1 kcal/mol (−6.4 ± 0.9, monomer). (Reprinted with permission from Reference . Copyright 2017 American Chemical Society)
[ Normal View | Magnified View ]
One‐pot consecutive two‐enzyme sequential cascade. 4‐Oxo‐pentenoate derivatives are first hydrogenated 4‐oxo‐pentanoate via enoate reductase (ER). The cis‐ or trans‐ of the precursors affect the anti‐ or syn‐configurations of the immediate products. The ketone is further reduced to hydroxyl group via alcohol dehydrogenase (ADH). ADH produced from various bacterial species such as Thermoanaerobacter sp. (ADHT) or Lactobacillus brevis (ADHLK) stereoselectively produces the alcohol semiproducts. The closure of lactone ring is achieved by simple acidification
[ Normal View | Magnified View ]
Engineering of CYP260A1 for stereoselective hydroxylation of progesterone. (a) S276 in the engineered enzyme corresponds to S326 in the native CYP260A1. S276I and S276N mutants selectively catalyze 1α‐ and 17α‐hydroxylation, respectively. (b) The binding mode of progesterone in S276I‐progesterone complex (PDB ID: 6F8C) corresponds to the predicted docking pose I. (c) The binding mode of progesterone in S276N‐progesterone complex (PDB ID: 6F88) corresponds to the predicted docking pose II
[ Normal View | Magnified View ]
Diels–Alder reaction. (a) The de novo designed diels‐alderase, DA_20_10, catalyzes the formation of nearly pure 3R,4S‐product. (b) True catalysis by ribozyme: the oligo(ethylene glycol) anthracene derivatives enters the active site via a wider opening. The resulting orientation favors the formation of R,R‐product. (c) Tethered catalysis: the anthracene moiety is tethered near the narrower backdoor openings on the ribozyme. A short ethylene glycol tether of 2–8 units long forces the substrate to enter the active site with opposite orientation, leading to S,S‐product
[ Normal View | Magnified View ]

Browse by Topic

Structure and Mechanism > Computational Biochemistry and Biophysics
Structure and Mechanism > Reaction Mechanisms and Catalysis
Molecular and Statistical Mechanics > Molecular Dynamics and Monte-Carlo Methods

Access to this WIREs title is by subscription only.

Recommend to Your
Librarian Now!

The latest WIREs articles in your inbox

Sign Up for Article Alerts