Inverting the enantioselectivity of a carbonyl reductase via substrate-enzyme docking-guided point mutation

Organic Letters
Dunming ZhuLing Hua

Abstract

Substrate-enzyme docking-guided point mutation of a carbonyl reductase from Sporobolomyces salmonicolor led to mutant enzymes, which reversed the enantiopreference and enhanced the enantioselectivity toward the reduction of para-substituted acetophenones. Such a dramatic change in the enantioselectivity indicates that the 245 residue in the catalytic site plays a critical role in determining the enantioselectivity of these ketone reductions, providing valuable insight into our understanding of how residues involved in substrate binding affect the orientation of bound substrate and thus control the reduction stereoselectivity.

References

Feb 1, 1995·Protein Engineering·A C WallaceJ M Thornton
Aug 2, 2000·Proceedings of the National Academy of Sciences of the United States of America·R H van Den HeuvelW J van Berkel
Mar 11, 2003·Proceedings of the National Academy of Sciences of the United States of America·Gavin J WilliamsAlan Berry
Jun 5, 2003·Proceedings of the National Academy of Sciences of the United States of America·Matthieu SchapiraHerbert H Samuels
Jun 27, 2003·Journal of Medicinal Chemistry·Matthieu SchapiraMaxim Totrov
Mar 11, 2005·Molecular & Cellular Proteomics : MCP·Jianghong AnRuben Abagyan
Jul 7, 2005·Angewandte Chemie·Roland WeisAnton Glieder
Dec 13, 2005·Chembiochem : a European Journal of Chemical Biology·Melloney J DrögeWim J Quax
Oct 27, 2006·The Journal of Organic Chemistry·Christopher M ClouthierManfred T Reetz

❮ Previous
Next ❯

Citations

Mar 9, 2013·Journal of Biotechnology·Andre JakoblinnertUlrich Schwaneberg
Apr 30, 2011·Chemical Reviews·Eduardo García-UrdialesVicente Gotor
Sep 18, 2015·Applied Microbiology and Biotechnology·Martina Letizia ContenteDiego Romano
Apr 26, 2011·Current Opinion in Biotechnology·Jürgen Pleiss
Jan 1, 2012·Computational and Structural Biotechnology Journal·Michael WidmannAnne K Samland
Oct 23, 2010·The Journal of Organic Chemistry·Hongmei LiKatherine Kantardjieff

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.