Multicopper oxidases (MCOs) use copper ions as cofactors to oxidize a variety of substrates while reducing oxygen to water. MCOs have been identified in various taxa, with notable occurrences in fungi. The role of these fungal MCOs in lignin degradation sparked an interest due to their potential for application in biofuel production and various other industries. MCOs consist of different protein domains, which led to their classification into two‐, three‐, and six‐domain MCOs. The previously established Laccase and Multicopper Oxidase Engineering Database (https://lcced.biocatnet.de) was updated and now includes 51 058 sequences and 229 structures of MCOs. Sequences and structures of all MCOs were systematically compared. All MCOs consist of cupredoxin‐like domains. Two‐domain MCOs are formed by the N‐ and C‐terminal domain (domain N and C), while three‐domain MCOs have an additional domain (M) in between, homologous to domain C. The six‐domain MCOs consist of alternating domains N and C, each three times. Two standard numbering schemes were developed for the copper‐binding domains N and C, which facilitated the identification of conserved positions and a comparison to previously reported results from mutagenesis studies. Two sequence motifs for the copper binding sites were identified per domain. Their modularity, depending on the placement of the T1‐copper binding site, was demonstrated. Protein sequence networks showed relationships between two‐ and three‐domain MCOs, allowing for family‐specific annotation and inference of evolutionary relationships.

中文翻译：

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铜氧化酶：模块结构，序列空间和进化关系。

Multicopper氧化酶（MCO）使用铜离子作为辅助因子来氧化多种底物，同时将氧气还原为水。已在各种生物分类中鉴定出MCO，在真菌中也有明显的发生。这些真菌MCO在木质素降解中的作用引起了人们的兴趣，原因是它们在生物燃料生产和其他各种工业中的应用潜力。MCO由不同的蛋白质结构域组成，这导致它们分为两，三和六结构域MCO。以前建立的漆酶和多铜氧化酶工程数据库（https://lcced.biocatnet.de）已更新，现在包括51 058个序列和229个MCO结构。系统比较了所有MCO的序列和结构。所有MCO均由类铜氧还蛋白域组成。两域MCO由N端和C端域（域N和C）组成，而三域MCO之间有一个额外的域（M），与域C同源。六域MCO由交替的域N和C组成，每三个域。针对铜结合域N和C，开发了两种标准的编号方案，这有助于鉴定保守位置并与先前报道的诱变研究结果进行比较。每个结构域鉴定出两个铜结合位点的序列基序。证明了它们的模块性，取决于T1铜结合位点的位置。蛋白质序列网络显示了两域和三域MCO之间的关系，从而可以进行家族特异性注释和推断进化关系。六个域的MCO由交替的域N和C组成，每三个域一次。针对铜结合域N和C，开发了两种标准的编号方案，这有助于鉴定保守位置并与先前报道的诱变研究结果进行比较。每个结构域鉴定出两个铜结合位点的序列基序。证明了它们的模块性，取决于T1铜结合位点的位置。蛋白质序列网络显示了两域和三域MCO之间的关系，从而可以进行家族特异性注释和推断进化关系。六个域的MCO由交替的域N和C组成，每三个域一次。针对铜结合域N和C，开发了两种标准的编号方案，这有助于鉴定保守位置并与先前报道的诱变研究结果进行比较。每个结构域鉴定出两个铜结合位点的序列基序。证明了它们的模块性，取决于T1铜结合位点的位置。蛋白质序列网络显示了两域和三域MCO之间的关系，从而可以进行家族特异性注释和推断进化关系。这有助于确定保守位置，并与诱变研究先前报道的结果进行比较。每个结构域鉴定出两个铜结合位点的序列基序。证明了它们的模块性，取决于T1铜结合位点的位置。蛋白质序列网络显示了两域和三域MCO之间的关系，从而可以进行家族特异性注释和推断进化关系。这有助于确定保守位置，并与诱变研究先前报道的结果进行比较。每个结构域鉴定出两个铜结合位点的序列基序。证明了它们的模块性，取决于T1铜结合位点的位置。蛋白质序列网络显示了两域和三域MCO之间的关系，从而可以进行家族特异性注释和推断进化关系。