NDLI: Computational Design and Elaboration of a De Novo Heterotetrameric α-Helical Protein that Selectively Binds an Emissive Abiological (Porphinato)zinc Chromophore

Content Provider	PubMed Central
Author	Fry, H. Christopher Lehmann, Andreas Saven, Jeffrey G. Degrado, William F. Therien, Michael J.
Abstract	The first example of a computationally de novo designed protein that binds an emissive abiological chromophore is presented, in which a sophisticated level of cofactor discrimination is pre-engineered. This heterotetrameric, C2 -symmetric bundle, AHis:BThr , uniquely binds (5,15-di[(4-carboxymethyleneoxy)phenyl]porphinato)zinc [ (DPP)Zn ] via histidine coordination and complementary noncovalent interactions. The A2B2 heterotetrameric protein reflects ligand-directed elements of both positive and negative design, including hydrogen-bonds to second-shell ligands. Experimental support for the appropriate formulation of [ (DPP)Zn:AHis:BThr ] 2 is provided by UV/visible and circular dichroism spectroscopies, size exclusion chromatography, and analytical ultracentrifugation. Time-resolved transient absorption and fluorescence spectroscopic data reveal classic excited-state singlet and triplet PZn photophysics for the AHis:BThr:(DPP)Zn protein (kfluorescence = 4 × 108 s−1; τ riplet = 5 ms). The A2B2 apoprotein has immeasurably low binding affinities for related [porphinato]metal chromophores that include a (DPP)Fe(III) cofactor and the zinc metal ion hemin derivative [ (PPIX)Zn ], underscoring the exquisite active site binding discrimination realized in this computationally designed protein. Importantly, elements of design in the AHis:Bthr protein ensure that interactions within the tetra-α-helical bundle are such that only the heterotetramer is stable in solution; corresponding homomeric bundles present unfavorable ligand-binding environments, and thus preclude protein structural rearrangements that could lead to binding of (porphinato)iron cofactors.
Related Links	http://dx.doi.org/10.1021/ja907407m
Ending Page	4005
Page Count	9
Starting Page	3997
File Format	PDF
ISSN	00027863
e-ISSN	15205126
Journal	Journal of the American Chemical Society
Issue Number	11
Volume Number	132
Language	English
Publisher Date	2010-03-24
Access Restriction	Open
Subject Keyword	Colloid and Surface Chemistry Biochemistry Chemistry(all) Catalysis Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Chemistry Colloid and Surface Chemistry Biochemistry Catalysis

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1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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