Artificial Metalloproteins with Dinuclear Iron–Hydroxido Centers

Miller, Kent R.; Biswas, Sabyasachi; Jasniewski, Andrew J.; Follmer, Alec H.; Biswas, Ankita; Albert, Therese; Sabuncu, Sinan; Bominaar, Emile L.; Hendrich, Michael P.; Moënne‐Loccoz, Pierre; Borovik, A. S.

doi:10.1021/jacs.0c12564

Cited by 12 publications

(15 citation statements)

References 83 publications

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“…Despite the ubiquitous nature of natural (μ-carboxylato)diiron enzymes, there are few examples of incorporating such an active site into an ArM due to the difficulty involved in tailoring a binding environment for not one but two metal centers. The de novo Due Ferri (DF) scaffold designed by Lombardi, DeGrado, and co-workers has proven to be extremely valuable for the generation and study of such active sites and is discussed in depth by Pecoraro and co-workers. − Recently, the Sav-biotin system was reengineered to form a unique (μ-carboxylato)diiron binding site, employing a combination of Trojan Horse and direct AA coordination approaches . To do so, Borovik and co-workers took advantage of the quaternary structure of Sav, which positions two biotin-binding sites in close proximity and with an intermediary pocket.…”

Section: Catalysis Beyond the Primary Coordination Sphere By Designed...mentioning

confidence: 99%

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Designing Artificial Metalloenzymes by Tuning of the Environment beyond the Primary Coordination Sphere

et al. 2022

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Metalloenzymes catalyze a variety of reactions using a limited number of natural amino acids and metallocofactors. Therefore, the environment beyond the primary coordination sphere must play an important role in both conferring and tuning their phenomenal catalytic properties, enabling active sites with otherwise similar primary coordination environments to perform a diverse array of biological functions. However, since the interactions beyond the primary coordination sphere are numerous and weak, it has been difficult to pinpoint structural features responsible for the tuning of activities of native enzymes. Designing artificial metalloenzymes (ArMs) offers an excellent basis to elucidate the roles of these interactions and to further develop practical biological catalysts. In this review, we highlight how the secondary coordination spheres of ArMs influence metal binding and catalysis, with particular focus on the use of native protein scaffolds as templates for the design of ArMs by either rational design aided by computational modeling, directed evolution, or a combination of both approaches. In describing successes in designing heme, nonheme Fe, and Cu metalloenzymes, heteronuclear metalloenzymes containing heme, and those ArMs containing other metal centers (including those with non-native metal ions and metallocofactors), we have summarized insights gained on how careful controls of the interactions in the secondary coordination sphere, including hydrophobic and hydrogen bonding interactions, allow the generation and tuning of these respective systems to approach, rival, and, in a few cases, exceed those of native enzymes. We have also provided an outlook on the remaining challenges in the field and future directions that will allow for a deeper understanding of the secondary coordination sphere a deeper understanding of the secondary coordintion sphere to be gained, and in turn to guide the design of a broader and more efficient variety of ArMs.

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Section: Catalysis Beyond the Primary Coordination Sphere By Designed...mentioning

confidence: 99%

“…PCS residues are highlighted as light gray, and SCS in light blue (PDB ID: 6VP1). Atom coloring: N (blue); O (red); S (yellow); Fe (orange).…”

Section: Catalysis Beyond the Primary Coordination Sphere By Designed...mentioning

confidence: 99%

Designing Artificial Metalloenzymes by Tuning of the Environment beyond the Primary Coordination Sphere

et al. 2022

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“…Biotinylated dipyridylmethylamine (dpa) ligands containing variable ethyl, propyl, or butyl linkers were used to synthesize the Fe complexes [Fe III (biot-n-dpa)(OH 2 ) 3 ]Cl 3 (n = Et, Pr, Bu), and a series of Sav variants (S112Y, K121Y, and K121A/L124Y) containing tyrosine mutations were selected with the intention of providing a readily visible optical assay for amino acid binding due to Fe III –O Y interactions ( Figure 13 ). 88 Incubation of the complexes in the Sav variants resulted in the observation of an intense blue color (λ max = 605 nm, ε M = 2800 M –1 cm –1 ) indicative of formation of an Fe III –O Y bond for only [Fe III (biot-bu-dpa)]⊂K121A/L124Y-Sav. Binding of the tyrosinate moiety to the Fe III center was further supported by the observation of characteristic phenol ring vibrations and ν(Fe–O Y ) and ν(C–O Y ) modes for Fe III -bound tyrosinate species by resonance Raman spectroscopy.…”

Section: Re-engineering Proteins Into Armsmentioning

confidence: 99%

Artificial Metalloproteins: At the Interface between Biology and Chemistry

Kerns

Biswas

Minnetian

et al. 2022

JACS Au

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Artificial metalloproteins (ArMs) have recently gained significant interest due to their potential to address issues in a broad scope of applications, including biocatalysis, biotechnology, protein assembly, and model chemistry. ArMs are assembled by the incorporation of a non-native metallocofactor into a protein scaffold. This can be achieved by a number of methods that apply tools of chemical biology, computational de novo design, and synthetic chemistry. In this Perspective, we highlight select systems in the hope of demonstrating the breadth of ArM design strategies and applications and emphasize how these systems address problems that are otherwise difficult to do so with strictly biochemical or synthetic approaches.

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“…111,153 We note, however, that there are many examples in which synthetic complexes have been inserted into proteins (i.e., artificial metalloenzymes) or synthetic scaffolds (e.g., zeolites), and the environment around the complexes has been shown to play an important role in tuning the chemo-, regio-, site-, and enantioselectivity during catalysis. [154][155][156][157][158][159] High-resolution single-crystal X-ray diffraction has revealed that carbon monoxide, a molecule that inhibits FeMo-cofactor, replaces the belt sulfur atom at 2B position (S2B) in FeMocofactor. 37 The lability of the belt sulfide in FeMo-cofactor inspired the idea to substitute S2B with Se due to its spectroscopic properties by the addition of KSeCN under proton-reducing turnover conditions.…”

Section: Reactivity Of Extracted Femo-cofactormentioning

confidence: 99%