Design and characterisation of an artificial DNA-binding cytochrome

Chembiochem : a European Journal of Chemical Biology
D Dafydd Jones, Paul D Barker

Abstract

We aim to design novel proteins that link specific biochemical binding events, such as DNA recognition, with electron transfer functionality. We want these proteins to form the basis of new molecules that can be used for templated assembly of conducting cofactors or for thermodynamically linking DNA binding with cofactor chemistry for nanodevice applications. The first examples of our new proteins recruit the DNA-binding basic helix region of the leucine zipper protein GCN4. This basic helix region was attached to the N and C termini of cytochrome b(562) (cyt b(562)) to produce new, monomeric, multifunctional polypeptides. We have fully characterised the DNA and haem-binding properties of these proteins, which is a prerequisite for future application of the new molecules. Attachment of a single basic helix of GCN4 to either the N or C terminus of the cytochrome does not result in specific DNA binding but the presence of DNA-binding domains at both termini converts the cytochrome into a specific DNA-binding protein. Upon binding haem, this chimeric protein attains the spectral characteristics of wild-type cyt b(562). The three forms of the protein, apo, oxidised holo and reduced holo, all bind the designed (ATGAcgATGA) target DN...Continue Reading

References

Oct 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·C ParkW A Goddard
Aug 17, 1990·Science·R V TalanianP S Kim
Nov 21, 1995·Biochemistry·P D BarkerI M Fearnley
Jan 1, 1994·Nature Structural Biology·Y FengA J Wand
Apr 14, 1995·Journal of Molecular Biology·K HamadaF S Mathews
Feb 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·B Cuenoud, A Schepartz
Jun 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·C ParkW A Goddard
Sep 18, 1997·Proceedings of the National Academy of Sciences of the United States of America·H W Hellinga
Oct 23, 1997·Proceedings of the National Academy of Sciences of the United States of America·D ShelverG P Roberts
Jun 17, 1998·Nature Structural Biology·P B RupertB W Matthews
Jul 17, 1998·Nature Structural Biology·H W Hellinga
Jul 7, 1999·Biochemistry·F ArnesanoA R Fersht
Jun 7, 2000·Proceedings of the National Academy of Sciences of the United States of America·D E BensonH W Hellinga
Oct 4, 2000·Nature Structural Biology·W N LanzilottaT L Poulos
Apr 26, 2001·Proceedings of the National Academy of Sciences of the United States of America·J S Marvin, H W Hellinga
Dec 14, 2001·Molecular Cell·C W Garvie, C Wolberger
Aug 7, 2002·Current Opinion in Structural Biology·Laura S Mizoue, Walter J Chazin

❮ Previous
Next ❯

Citations

Nov 18, 2011·ACS Nano·Eduardo Antonio Della PiaJ Emyr Macdonald
Sep 21, 2012·Chemical Communications : Chem Comm·Eduardo Antonio Della PiaD Dafydd Jones
Aug 2, 2014·Acta Crystallographica. Section D, Biological Crystallography·James A J ArpinoD Dafydd Jones
Mar 19, 2020·Chemical Communications : Chem Comm·Benjamin J BowenD Dafydd Jones
May 5, 2005·Journal of the American Chemical Society·Yogendra SinghDavid P Fairlie

❮ 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.