7B74

Chimeric Streptavidin With A Dimerization Domain For Artificial Transfer Hydrogenation

This is a non-PDB format compatible entry.

Summary for 7B74

• Entry DOI: 10.2210/pdb7b74/pdb
• Descriptor: Streptavidin,Superoxide dismutase [Cu-Zn],Streptavidin, {N-(4-{[2-(amino-kappaN)ethyl]sulfamoyl-kappaN}phenyl)-5-[(3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl]pentanamide}(chloro)[(1,2,3,4,5-eta)-1,2,3,4,5-pentamethylcyclopentadienyl]iridium(III) (3 entities in total)
• Functional Keywords: artificial tranfer hydrogenation biotin-binding protein artificial metalloenzyme, metal binding protein
• Biological source: Streptomyces avidinii; More
• Total number of polymer chains: 4
• Total formula weight: 83677.22

Authors

Igareta, N.V.,Ward, T.R. (deposition date: 2020-12-09, release date: 2021-11-17, Last modification date: 2024-02-07)

Primary citation

Igareta, N.V.,Tachibana, R.,Spiess, D.C.,Peterson, R.L.,Ward, T.R.
Spiers Memorial Lecture: Shielding the active site: a streptavidin superoxide-dismutase chimera as a host protein for asymmetric transfer hydrogenation.
Faraday Disc.Chem.Soc, 2023

PubMed Abstract: By anchoring a metal cofactor within a host protein, so-called artificial metalloenzymes can be generated. Such hybrid catalysts combine the versatility of transition metals in catalyzing new-to-nature reactions with the power of genetic-engineering to evolve proteins. With the aim of gaining better control over second coordination-sphere interactions between a streptavidin host-protein (Sav) and a biotinylated cofactor, we engineered a hydrophobic dimerization domain, borrowed from superoxide dismutase C (SOD), on Sav's biotin-binding vestibule. The influence of the SOD dimerization domain (DD) on the performance of an asymmetric transfer hydrogenase (ATHase) resulting from anchoring a biotinylated Cp*Ir-cofactor - [Cp*Ir(biot--L)Cl] (1-Cl) - within Sav-SOD is reported herein. We show that, depending on the nature of the residue at position Sav S112, the introduction of the SOD DD on the biotin-binding vestibule leads to an inversion of configuration of the reduction product, as well as a fivefold increase in catalytic efficiency. The findings are rationalized by QM/MM calculations, combined with X-ray crystallography.

PubMed: 36924204
DOI: 10.1039/d3fd00034f

Experimental method

X-RAY DIFFRACTION (1.85 Å)