Pope Sarah R, McBride Molly J, Nair Mrutyunjay A, Salas-Solá Xavier E, Krebs Carsten, Bollinger J Martin, Boal Amie K
Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, Pennsylvania, USA; email:
Department of Chemistry, The Pennsylvania State University, University Park, Pennsylvania, USA.
Annu Rev Biochem. 2025 Jun;94(1):59-88. doi: 10.1146/annurev-biochem-030122-043608. Epub 2025 Mar 27.
Heme oxygenase (HO)-like metalloenzymes are an emerging protein superfamily diverse in reaction outcome and mechanism. Found primarily in bacterial biosynthetic pathways, members conserve a flexible protein scaffold shared with the heme catabolic enzyme, HO, and a set of metal-binding residues. Most HO-like metalloenzymes assemble a diiron cluster, although manganese-iron and mononuclear iron cofactors can also be accommodated. In the canonical HO-like diiron oxygenases/oxidases (HDOs), an Fe(II/II) complex reacts with O to form a peroxo-Fe(III/III) intermediate (), common to all HDOs studied to date. The HO-like scaffold confers both distinctive metal-binding properties, allowing for dynamic cofactor assembly and disassembly, and unusual reactivity to its associated metallocofactor. These features may prove to be important in HDO-mediated catalysis of the fragmentation and rearrangement reactions that remain unprecedented among other dinuclear iron enzymes. Much of the sequence space in the HO-like metalloenzyme superfamily remains unexplored, offering exciting opportunities for the discovery of new mechanisms and reactivities.
血红素加氧酶（HO）样金属酶是一个新兴的蛋白质超家族，其反应结果和机制各不相同。它们主要存在于细菌生物合成途径中，成员保留了与血红素分解代谢酶HO共有的灵活蛋白质支架以及一组金属结合残基。大多数HO样金属酶组装一个双铁簇，不过锰铁和单核铁辅因子也能被容纳。在典型的HO样双铁加氧酶/氧化酶（HDO）中，一个Fe（II/II）复合物与O反应形成一个过氧-Fe（III/III）中间体（），这是迄今为止所有已研究的HDO所共有的。HO样支架赋予了独特的金属结合特性，允许动态辅因子组装和拆卸，并赋予其相关金属辅因子不同寻常的反应活性。这些特性可能在HDO介导的碎片化和重排反应催化中很重要，而这些反应在其他双核铁酶中是前所未有的。HO样金属酶超家族中的大部分序列空间仍未被探索，为发现新机制和反应活性提供了令人兴奋的机会。
