21 publications

21 publications

A Designed Functional Metalloenzyme that Reduces O2 to H2O with Over One Thousand Turnovers

Lu, Y.

Angew. Chem., Int. Ed., 2012, 10.1002/anie.201201981

Rational design of functional enzymes with a high number of turnovers is a challenge, especially those with a complex active site, such as respiratory oxidases. Introducing two His and one Tyr residues into myoglobin resulted in enzymes that reduce O2 to H2O with more than 1000 turnovers (red line, see scheme) and minimal release of reactive oxygen species. The positioning of the Tyr residue is critical for activity.


Metal: Cu
Ligand type: Amino acid
Host protein: Myoglobin (Mb)
Anchoring strategy: Dative
Optimization: Chemical & genetic
Max TON: 1056
ee: ---
PDB: 4FWX
Notes: Sperm whale myoglobin

Alteration of the Oxygen-Dependent Reactivity of De Novo Due Ferri Proteins

DeGrado, W. F.

Nat. Chem., 2012, 10.1038/NCHEM.1454

De novo proteins provide a unique opportunity to investigate the structure–function relationships of metalloproteins in a minimal, well-defined and controlled scaffold. Here, we describe the rational programming of function in a de novo designed di-iron carboxylate protein from the Due Ferri family. Originally created to catalyse the O2-dependent, two-electron oxidation of hydroquinones, the protein was reprogrammed to catalyse the selective N-hydroxylation of arylamines by remodelling the substrate access cavity and introducing a critical third His ligand to the metal-binding cavity. Additional second- and third-shell modifications were required to stabilize the His ligand in the core of the protein. These structural changes resulted in at least a 106-fold increase in the relative rate between the arylamine N-hydroxylation and hydroquinone oxidation reactions. This result highlights the potential for using de novo proteins as scaffolds for future investigations of the geometric and electronic factors that influence the catalytic tuning of di-iron active sites.


Metal: Fe
Ligand type: Amino acid
Host protein: Due Ferro 1
Anchoring strategy: Dative
Optimization: Genetic
Reaction: N-Hydroxylation
Max TON: ---
ee: ---
PDB: 2LFD
Notes: ---

A Rhodium Complex-Linked β-Barrel Protein as a Hybrid Biocatalyst for Phenylacetylene Polymerization

Hayashi, T

Chem. Commun., 2012, 10.1039/C2CC35165J

Our group recently prepared a hybrid catalyst containing a rhodium complex, Rh(Cp)(cod), with a maleimide moiety at the peripheral position of the Cp ligand. This compound was then inserted into a β-barrel protein scaffold of a mutant of aponitrobindin (Q96C) via a covalent linkage. The hybrid protein is found to act as a polymerization catalyst and preferentially yields trans-poly(phenylacetylene) (PPA), although the rhodium complex without the protein scaffold normally produces cis PPA.


Metal: Rh
Ligand type: COD; Cp*
Host protein: Nitrobindin (Nb)
Anchoring strategy: Cystein-maleimide
Optimization: ---
Max TON: ---
ee: ---
PDB: ---
Notes: ---

Artificial Copper Enzymes for Asymmetric Diels–AlderReactions

Kamer, P. C. J.; Laan, W.

ChemCatChem, 2012, 10.1002/cctc.201200671


Metal: Cu
Anchoring strategy: Covalent
Optimization: Chemical & genetic
Max TON: 9.6
ee: 25
PDB: 1IKT
Notes: ---

Artificial Dicopper Oxidase: Rational Reprogramming of Bacterial Metallo- b-lactamase into a Catechol Oxidase

Fujieda, N.; Itoh, S.

Chem. - Asian J., 2012, 10.1002/asia.201101014


Metal: Cu
Ligand type: Amino acid
Host protein: β-lactamase
Anchoring strategy: Dative
Optimization: Genetic
Reaction: Catechol oxidation
Max TON: ---
ee: ---
PDB: 2FU7
Notes: ---

Artificial Enzymes Based on Supramolecular Scaffolds

Review

Liu, J.

Chem. Soc. Rev., 2012, 10.1039/c2cs35207a


Notes: ---

Artificial Metalloenzymes as Catalysts in Stereoselective Diels–Alder Reactions

Review

Reetz, M. T.

Chem. Rec., 2012, 10.1002/tcr.201100043


Notes: ---

Biotinylated Rh(III) Complexes in Engineered Streptavidin for Accelerated Asymmetric C–H Activation

Rovis, T.; Ward, T. R.

Science, 2012, 10.1126/science.1226132


Metal: Rh
Ligand type: Amino acid; Cp*
Host protein: Streptavidin (Sav)
Anchoring strategy: Supramolecular
Optimization: Genetic
Reaction: C-H activation
Max TON: 95
ee: 82
PDB: ---
Notes: ---

Catalysis by a De Novo Zinc-Mediated Protein Interface: Implications for Natural Enzyme Evolution and Rational Enzyme Engineering

Kuhlman, B.

Biochemistry, 2012, 10.1021/bi201881p


Metal: Zn
Ligand type: Amino acid
Anchoring strategy: Dative
Optimization: Chemical & genetic
Max TON: >50
ee: ---
PDB: 3V1C
Notes: ---

Computational Redesign of a Mononuclear Zinc Metalloenzyme for Organophosphate Hydrolysis

Baker, D.

Nat. Chem. Biol., 2012, 10.1038/NChemBio.777


Metal: Zn
Ligand type: Amino acid
Anchoring strategy: Dative
Optimization: Genetic
Max TON: >140
ee: ---
PDB: 3T1G
Notes: kcat/KM ≈ 104 M-1*s-1

Creation of an Artificial Metalloprotein with a Hoveyda–Grubbs Catalyst Moiety through the Intrinsic Inhibition Mechanism of α-Chymotrypsin

Chem. Commun., 2012, 10.1039/c2cc16898g


Metal: Ru
Ligand type: Carbene
Host protein: α-chymotrypsin
Anchoring strategy: Covalent
Optimization: ---
Reaction: Olefin metathesis
Max TON: 20
ee: ---
PDB: ---
Notes: RCM

Crystal Structure of Two Anti-Porphyrin Antibodies with Peroxidase Activity

Golinelli-Pimpaneau, B.

Plos ONE, 2012, 10.1371/journal.pone.0051128


Metal: Fe
Ligand type: Porphyrin
Host protein: Antibody 13G10
Anchoring strategy: Antibody
Optimization: Chemical & genetic
Reaction: Peroxidation
Max TON: ---
ee: ---
PDB: 4AMK
Notes: ---

Metal: Fe
Ligand type: Porphyrin
Host protein: Antibody 14H7
Anchoring strategy: Antibody
Optimization: Chemical & genetic
Reaction: Peroxidation
Max TON: ---
ee: ---
PDB: 4AT6
Notes: ---

Design and Evolution of Artificial Metalloenzymes: Biomimetic Aspects

Review

Creus, M.; Ward, T. R.

Prog. Inorg. Chem., 2012, 10.1002/9781118148235.ch4


Notes: ---

Designing a Functional Type 2 Copper Center that has Nitrite Reductase Activity Within α-Helical Coiled Coils

Pecoraro, V. L.

Proc. Natl. Acad. Sci. U. S. A., 2012, 10.1073/pnas.1212893110


Metal: Cu
Ligand type: Amino acid
Host protein: TRI peptide
Anchoring strategy: Dative
Optimization: Chemical & genetic
Max TON: >5
ee: ---
PDB: ---
Notes: Nitrite reduction

Enantioselective Artificial Metalloenzymes by Creation of a Novel Active Site at the Protein Dimer Interface

Roelfes, G.

Angew. Chem., Int. Ed., 2012, 10.1002/anie.201202070


Metal: Cu
Ligand type: Bipyridine; Phenanthroline
Host protein: LmrR
Anchoring strategy: Covalent
Optimization: Genetic
Max TON: 32.7
ee: 97
PDB: 3F8B
Notes: ---

Enantioselective Transfer Hydrogenation of Ketone Catalysed by Artificial Metalloenzymes Derived from Bovine β-Lactoglobulin

Salmain, M.

Chem. Commun., 2012, 10.1039/c2cc36980j


Metal: Rh
Ligand type: Cp*; Poly-pyridine
Host protein: ß-lactoglobulin
Anchoring strategy: Supramolecular
Optimization: Chemical
Reaction: Hydrogenation
Max TON: 34
ee: 26
PDB: ---
Notes: ---

Incorporation of Manganese Complexes into Xylanase: New Artificial Metalloenzymes for Enantioselective Epoxidation

Mahy, J.-P.; Ricoux, R.

ChemBioChem, 2012, 10.1002/cbic.201100659


Metal: Mn
Ligand type: Porphyrin
Host protein: Xylanase A (XynA)
Anchoring strategy: Supramolecular
Optimization: ---
Reaction: Epoxidation
Max TON: 21
ee: 80
PDB: ---
Notes: ---

Organometallic Chemistry in Protein Scaffolds

Review

Ward, T. R.

Protein Engineering Handbook, 2012, ISBN: 978-3-527-33123-9


Notes: Book chapter

Semi-Synthesis of an Artificial Scandium(III) Enzyme with a β-Helical Bio-Nanotube

Ueno, T.

Dalton Trans., 2012, 10.1039/C2DT31030A


Metal: Sc
Ligand type: Bipyridine
Host protein: [(gp5βf)3]2
Anchoring strategy: Cystein-maleimide
Optimization: Genetic
Max TON: ---
ee: ---
PDB: ---
Notes: ---

Significant Increase of Oxidase Activity through the Genetic Incorporation of a Tyrosine–Histidine Cross-Link in a Myoglobin Model of Heme–Copper Oxidase

Lu, Y.; Wang, J.

Angew. Chem., Int. Ed., 2012, 10.1002/anie.201108756


Metal: Cu
Ligand type: Amino acid
Host protein: Myoglobin (Mb)
Anchoring strategy: Dative
Optimization: Chemical & genetic
Max TON: 1100
ee: ---
PDB: ---
Notes: Sperm whale myoglobin

Structure and Dynamics of a Primordial Catalytic fold Generated by In Vitro Evolution

Seelig, B.

Nat. Chem. Biol., 2012, 10.1038/nchembio.1138


Metal: Zn
Ligand type: Amino acid
Anchoring strategy: Dative
Optimization: Genetic
Reaction: RNA ligation
Max TON: ---
ee: ---
PDB: 2LZE
Notes: ---