Computational de novo design and characterization of a four-helix bundle protein that selectively binds a nonbiological cofactor.

Computational de novo design and characterization of a four-helix bundle protein that selectively binds a nonbiological cofactor. Research Abstract Details 

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Computational de novo design and characterization of a four-helix bundle protein that selectively binds a nonbiological cofactor. Abstract Text:

Frank V Cochran,Sophia P Wu,Wei Wang,Vikas Nanda,Jeffery G Saven,Michael J Therien,William F DeGrado,

We report the complete de novo design of a four-helix bundle protein that selectively binds the nonbiological DPP-Fe(III) metalloporphyrin cofactor (DPP-Fe(III) = 5, 15-Di[(4-carboxymethyleneoxy)phenyl]porphinato iron(III)). A tetrameric, D2-symmetric backbone scaffold was constructed to encapsulate two DPP-Fe(III) units through bis(His) coordination. The complete sequence was determined with the aid of the statistical computational design algorithm SCADS. The 34-residue peptide was chemically synthesized. UV-vis and CD spectroscopy, size-exclusion chromatography, and analytical ultracentrifugation indicated the peptide undergoes a transition from a predominantly random coil monomer to an alpha-helical tetramer upon binding DPP-Fe(III). EPR spectroscopy studies indicated the axial imidazole ligands were oriented in a perpendicular fashion, as defined by second-shell interactions that were included in the design. The 1-D 1H NMR spectrum of the assembled protein displayed features of a well-packed interior. The assembled protein possessed functional redox properties different from those of structurally similar systems containing the heme cofactor. The designed peptide demonstrated remarkable cofactor selectivity with a significantly weaker binding affinity for the natural heme cofactor. These findings open a path for the selective incorporation of more elaborate cofactors into designed scaffolds for constructing molecularly well-defined nanoscale materials.

Computational de novo design and characterization of a four-helix bundle protein that selectively binds a nonbiological cofactor. Publishing Authors By Initials

FV Cochran,SP Wu,W Wang,V Nanda,JG Saven,MJ Therien,WF DeGrado,

For similar investigative techniques: chemistry, analytical: photometry: spectrophotometry: spectrophotometry, ultraviolet research abstracts see: investigative techniques: chemistry, analytical: photometry: spectrophotometry: spectrophotometry, ultraviolet research

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Computational de novo design and characterization of a four-helix bundle protein that selectively binds a nonbiological cofactor. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: Journal of the American Chemical Society

VOLUME: 127

Page Numbers: 1346-7

Journal Abbreviation: J. Am. Chem. Soc.

ISSN: 0002-7863

DAY: 9

MONTH: Feb

YEAR: 2005

Computational de novo design and characterization of a four-helix bundle protein that selectively binds a nonbiological cofactor. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 7503056

Computational de novo design and characterization of a four-helix bundle protein that selectively binds a nonbiological cofactor. Keywords Mesh Terms:

KEYWORDS: Spectrophotometry, Ultraviolet

MESH TERMS: chemistry

Chemical & Substance for Abstract: Computational de novo design and characterization of a four-helix bundle protein that selectively binds a nonbiological cofactor. Information

Substance Name: Heme

Registry Number: 14875-96-8

Grant and Affiliation Information for Computational de novo design and characterization of a four-helix bundle protein that selectively binds a nonbiological cofactor.

AFFILIATION: Department of Biochemistry and Molecular Biophysics, Johnson Foundation, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Country: United States

AGENCY: United States NIGMS

GRANT: GM61267

ACRONYM: GM

MEDLINETA: J Am Chem Soc

REFSOURCE: J Am Chem Soc. 2006 Jan 18;128(2):663

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