The Reaction Mechanisms of Zinc Enzymes

Schürer, Gudrun; Clark, Timothy; Eldik, Rudi van

doi:10.1002/9780470682531.pat0364

Cited by 1 publication

(1 citation statement)

References 268 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Zn(II) ions serve as powerful catalysts in many hydrolase enzymes with diverse, though generally related, mechanisms. 37 , 49 , 50 The reactivity of Zn(II) in enzymes centers around a Zn–OH 2 moiety (Figure 3 ). In the most common mechanism, the Lewis acidic Zn(II) center simply promotes deprotonation of the coordinated water to generate a hydroxide species at neutral pH (as in the mechanism for CA 24 , 51 , 52 ).…”

Section: Zn(ii) As An Attractive Catalyst In Proteinsmentioning

confidence: 99%

Designing Hydrolytic Zinc Metalloenzymes

2014

View full text Add to dashboard Cite

Zinc is an essential element required for the function of more than 300 enzymes spanning all classes. Despite years of dedicated study, questions regarding the connections between primary and secondary metal ligands and protein structure and function remain unanswered, despite numerous mechanistic, structural, biochemical, and synthetic model studies. Protein design is a powerful strategy for reproducing native metal sites that may be applied to answering some of these questions and subsequently generating novel zinc enzymes. From examination of the earliest design studies introducing simple Zn(II)-binding sites into de novo and natural protein scaffolds to current studies involving the preparation of efficient hydrolytic zinc sites, it is increasingly likely that protein design will achieve reaction rates previously thought possible only for native enzymes. This Current Topic will review the design and redesign of Zn(II)-binding sites in de novo-designed proteins and native protein scaffolds toward the preparation of catalytic hydrolytic sites. After discussing the preparation of Zn(II)-binding sites in various scaffolds, we will describe relevant examples for reengineering existing zinc sites to generate new or altered catalytic activities. Then, we will describe our work on the preparation of a de novo-designed hydrolytic zinc site in detail and present comparisons to related designed zinc sites. Collectively, these studies demonstrate the significant progress being made toward building zinc metalloenzymes from the bottom up.

show abstract