Submission Date


Document Type

Paper- Restricted to Campus Access



Faculty Mentor

Amanda Reig


Presented during the 20th Annual Summer Fellows Symposium, July 20, 2018 at Ursinus College.

Supported by a National Institutes of Health Academic Research Enhancement Award (AREA) grant (R15-GM110657) and the National Science Foundation (NSF) grant (MRI-1725534)

Project Description

Nearly half of all known proteins contain metal cofactors that impart unique structural changes on the polypeptide backbone. This allows the metalloprotein to accomplish functions that would not otherwise be possible in its non-metal state. Copper is one of the most common elements found in metalloproteins because of its high natural abundance and ability to perform reduction-oxidation (redox) reactions. Since copper proteins have been implicated in neurodegenerative diseases like ALS, Parkinson’s, and Alzheimer’s disease, understanding the structure-function relationship of copper metalloproteins is of particular interest. Coupled Binuclear Copper (CBC) proteins, such as haemocyanins, tyrosinases, and catechol oxidases, have two copper atoms each coordinated by three histidine residues in a tetrahedral geometry and a bridging oxygen ligand in the active site. These CBC proteins are involved in important processes like fruit browning, skin pigmentation, and oxygen activation and transport. To investigate the structure-function relationship of CBC proteins, a non-heme diiron protein model called due ferri single chain (DFsc) was adapted and used as a model for CBC proteins. Previously, a library of eight DFsc mutants with between two and six histidine residues were created; however, the six His model does not possess a tetrahedral active site. This study aims to create another six His model with a tetrahedral active site to access how active site geometry affects protein function and also seeks to complete the spectroscopic characterization and reactivity of the other variants.


Available to Ursinus community only.