Computational design of a biologically active enzyme

Science
Mary A DwyerHomme W Hellinga

Abstract

Rational design of enzymes is a stringent test of our understanding of protein chemistry and has numerous potential applications. Here, we present and experimentally validate the computational design of enzyme activity in proteins of known structure. We have predicted mutations that introduce triose phosphate isomerase activity into ribose-binding protein, a receptor that normally lacks enzyme activity. The resulting designs contain 18 to 22 mutations, exhibit 10(5)- to 10(6)-fold rate enhancements over the uncatalyzed reaction, and are biologically active, in that they support the growth of Escherichia coli under gluconeogenic conditions. The inherent generality of the design method suggests that many enzymes can be designed by this approach.

References

May 5, 1992·Journal of Molecular Biology·S L Mowbray, L B Cole
Mar 14, 1991·Nature·J R Knowles
Jan 1, 1986·Annual Review of Biochemistry·D G Fraenkel
Sep 11, 1998·Archives of Microbiology·G P FergusonI R Booth
Sep 25, 1998·The Journal of Biological Chemistry·W W ClelandJ A Gerlt
Aug 31, 2000·Annual Review of Biochemistry·D Hilvert
Dec 12, 2001·Current Opinion in Chemical Biology·J P Richard, T L Amyes
Dec 19, 2001·Accounts of Chemical Research·R Wolfenden, M J Snider
Jun 1, 2002·Current Opinion in Chemical Biology·Daniel N BolonStephen L Mayo
Oct 17, 2002·Protein Science : a Publication of the Protein Society·Robert M de LorimierHomme W Hellinga
Jan 2, 2003·Proceedings of the National Academy of Sciences of the United States of America·Gerwald JoglLiang Tong
Jan 11, 2003·The Journal of Biological Chemistry·Inari Kursula, Rik K Wierenga
May 9, 2003·Nature·Loren L LoogerHomme W Hellinga
Aug 30, 2003·Science·Stephen J Benkovic, Sharon Hammes-Schiffer
Sep 23, 2003·Proceedings of the National Academy of Sciences of the United States of America·M A DwyerH W Hellinga
Nov 25, 2003·Science·Brian KuhlmanDavid Baker
Jan 13, 2004·Science·Mireia Garcia-VilocaDonald G Truhlar

❮ Previous
Next ❯

Citations

Feb 9, 2005·Biopolymers·Jennifer R CalhounWilliam F DeGrado
Feb 3, 2007·Applied Microbiology and Biotechnology·Jürgen Pleiss
Apr 4, 2007·Applied Microbiology and Biotechnology·Matti Leisola, Ossi Turunen
Apr 7, 2005·Current Opinion in Chemical Biology·Jeremy MinshullSridhar Govindarajan
Apr 7, 2005·Current Opinion in Chemical Biology·Romas J Kazlauskas
Oct 16, 2009·Nature·Erika Check Hayden
Sep 24, 2005·Nature·William P RussRama Ranganathan
Mar 10, 2006·Nature Biotechnology·Frances H Arnold
Mar 9, 2007·Nature Biotechnology·Joelle N Pelletier, Robert Lortie
Sep 25, 2007·Nature Biotechnology·Shaun M LippowBruce Tidor
Jul 5, 2005·Nature Reviews. Genetics·Steven A Benner, A Michael Sismour
May 4, 2007·Chemical Communications : Chem Comm·Bernard T KellyAndrew D Griffiths
Sep 7, 2006·Bioinformatics·Matthias Heinemann, Sven Panke
Nov 30, 2006·Nucleic Acids Research·Andreas Martin Lisewski, Olivier Lichtarge
Dec 13, 2007·Nucleic Acids Research·Hiroshi ArakawaJean-Marie Buerstedde
Jan 26, 2007·Journal of the Royal Society, Interface·Philippe MarguetLingchong You
Nov 7, 2008·Molecular Pharmacology·Daquan GaoChang-Guo Zhan
May 10, 2005·Science·Aaron KorkegianBarry L Stoddard
Sep 9, 2005·Microbiology and Molecular Biology Reviews : MMBR·Ling YuanRobert Keenan
May 13, 2006·Annual Review of Biophysics and Biomolecular Structure·Glenn L Butterfoss, Brian Kuhlman
Mar 28, 2007·BMC Biotechnology·Jun LiaoJeremy Minshull
Oct 11, 2005·Microbial Cell Factories·Edward G Hibbert, Paul A Dalby
Jun 2, 2007·Genome Biology·Amy E Keating
Jul 15, 2006·PLoS Computational Biology·Feng Ding, Nikolay V Dokholyan
Aug 29, 2007·PLoS Computational Biology·Elisabeth L Humphris, Tanja Kortemme
Dec 3, 2008·The Journal of Chemical Physics·G OdriozolaM Lozada-Cassou
Apr 6, 2006·PLoS Biology·Christopher R OteyFrances H Arnold
Nov 1, 2006·Proceedings of the National Academy of Sciences of the United States of America·Jonathan Kyle LassilaStephen L Mayo
Aug 5, 2004·Proceedings of the National Academy of Sciences of the United States of America·J Kaplan, W F DeGrado
Mar 16, 2007·Proceedings of the National Academy of Sciences of the United States of America·Tong LiuVincent J Hilser
Jun 21, 2007·Proceedings of the National Academy of Sciences of the United States of America·Lauren M F MerloAntony M Dean
Aug 31, 2004·Proceedings of the National Academy of Sciences of the United States of America·Sofia HederosLars Baltzer
Mar 5, 2013·Annual Review of Biophysics·Zhixiu LiYaoqi Zhou
Dec 21, 2006·Proceedings of the National Academy of Sciences of the United States of America·Thomas P TreynorStephen L Mayo
Nov 9, 2006·Proceedings of the National Academy of Sciences of the United States of America·Pedro B CotoMassimo Olivucci
Jun 21, 2006·Proceedings of the National Academy of Sciences of the United States of America·Bryan T GreenhagenJoe Chappell
Feb 15, 2011·Journal of Molecular Modeling·Nicolò MazzuccoGiovanni Minervini
Jun 7, 2007·Organic & Biomolecular Chemistry·Marc Creus, Thomas R Ward
Mar 5, 2011·Organic & Biomolecular Chemistry·Xiaoqin HuangChang-Guo Zhan

❮ 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.

Related Papers

Proceedings of the National Academy of Sciences of the United States of America
Malin AllertHomme W Hellinga
Proceedings of the National Academy of Sciences of the United States of America
Daniel N Bolon, S L Mayo
© 2022 Meta ULC. All rights reserved