Related Experiment Video
Updated: Jun 25, 2026

X-Ray Crystallography to Study the Oligomeric State Transition of the Thermotoga maritima M42 Aminopeptidase TmPep1050
Published on: May 13, 2020
Crystal structure of a two-domain multicopper oxidase: implications for the evolution of multicopper blue proteins
Thomas J Lawton1, Luis A Sayavedra-Soto, Daniel J Arp
1Departments of Biochemistry, Molecular Biology, and Cell Biology and of Chemistry, Northwestern University, Evanston, Illinois 60208, USA.
Abstract:
The two-domain multicopper oxidases are proposed to be key intermediates in the evolution of three-domain multicopper oxidases. A number of two-domain multicopper oxidases have been identified from genome sequences and are classified as type A, type B, or type C on the basis of the predicted location of the type 1 copper center. The crystal structure of blue copper oxidase, a type C two-domain multicopper oxidase from Nitrosomonas europaea, has been determined to 1.9 A resolution. Blue copper oxidase is a trimer, of which each subunit comprises two cupredoxin domains. Each subunit houses a type 1 copper site in domain 1 and a type 2/type 3 trinuclear copper cluster at the subunit-subunit interface. The coordination geometry at the trinuclear copper site is consistent with reduction of the copper ions. Although the overall architecture of blue copper oxidase is similar to nitrite reductases, detailed structural alignments show that the fold and domain orientation more closely resemble the three-domain multicopper oxidases. These observations have important implications for the evolution of nitrite reductases and multicopper oxidases.
Related Concept Videos
Gene Duplication and Divergence
The duplicated copies of the gene are called Paralogs. Paralogs with similar sequences and functions form a gene family. Across several species, a large number of gene families are characterized.
Electron Transport Chain: Complex III and IV
Gene Families
Occasionally these regions can be adapted to take on new roles within the organism, becoming novel genes...
Protein and Protein Structure
A protein's shape is critical to its function. For example, an enzyme can...
Cooperative Allosteric Transitions
Cooperative Allosteric Transitions

