Catalysis and Electron Transfer in De Novo Designed Helical Scaffolds

Abstract

Keywords: enzymes ·h elical structures · metalloproteins · protein design · transition metals Angewandte Chemie Reviews 7678 www.angewandte.org

Stepwise nitrosylation of the nonheme iron site in an engineered azurin and a molecular basis for nitric oxide signaling mediated by nonheme iron proteins

“…Protein-based models and artificial metalloenzymes offer an alternative solution by constructing a metallo-center in a protein scaffold through the design of the coordination sphere. [32][33][34][35][36][37][38][39][40][41] Azurin (Az) has been demonstrated to be an excellent scaffold for engineering of chemical reactivity or catalytic function, as the engineered Az construct is more convenient to be expressed in E. coli rapidly (overnight) and with high yield (> 100 mg purified protein/L growth media), amenable to spectroscopic studies. [42][43][44][45][46] In this work, we have constructed {Fe(NO) 2 } 9 in an engineered Az scaffold and elucidated the stepwise nitrosylation pathway from {FeNO} 7 via {FeNO} 8 to {Fe(NO) 2 } 9 for the first time based on spectroscopic characterizations and DFT calculations.…”

Proteins as diverse, efficient, and evolvable scaffolds for artificial metalloenzymes

“…8A). 99 The peptides are templated by binding Hg 2+ , Cd 2+ , or Pb 2+ where other metal ions such as Zn and Cu play catalytic roles, such as in CO 2 hydration/ester hydrolysis 100,101 and nitrite reduction, 102,103 respectively. Alternatively, Fe 2+ can be incorporated into the a-helical structure, resulting in a rubredoxin-like protein, facilitating electron transfer.…”

The pH‐Induced Selectivity Between Cysteine or Histidine Coordinated Heme in an Artificial α‐Helical Metalloprotein

“…In particular, De Novo metalloprotein design has provided detailed insight into the relationship between the architecture of metal active sites and electron transfer or catalytic reactions [3] . In many cases, these synthetic systems utilize highly stable α‐helical scaffolds capable of binding a broad range of metals and metal cofactors (reviewed in [4] ). Among the most important and ubiquitous natural metalloenzymes are those containing the iron porphyrin cofactor, known as heme.…”