Lemaire Olivier N, Belhamri Mélissa, Wagner Tristan
Max Planck Institute for Marine Microbiology, Bremen, Germany.
Front Microbiol. 2023 May 11;14:1179204. doi: 10.3389/fmicb.2023.1179204. eCollection 2023.
Whilst widespread in the microbial world, the hybrid cluster protein (HCP) has been paradoxically a long-time riddle for microbiologists. During three decades, numerous studies on a few model organisms unravelled its structure and dissected its metal-containing catalyst, but the physiological function of the enzyme remained elusive. Recent studies on bacteria point towards a nitric oxide reductase activity involved in resistance during nitrate and nitrite reduction as well as host infection. In this study, we isolated and characterised a naturally highly produced HCP class I from a marine methanogenic archaeon grown on ammonia. The crystal structures of the enzyme in a reduced and partially oxidised state, obtained at a resolution of 1.45 and 1.36-Å, respectively, offered a precise picture of the archaeal enzyme intimacy. There are striking similarities with the well-studied enzymes from species regarding sequence, kinetic parameters, structure, catalyst conformations, and internal channelling systems. The close phylogenetic relationship between the enzymes from and many corroborates this similarity. Indeed, HCPs are closer to these bacterial homologues than to any other archaeal enzymes. The relatively high constitutive production of HCP in , in the absence of a notable nitric oxide source, questions the physiological function of the enzyme in these ancient anaerobes.
尽管杂合簇蛋白（HCP）在微生物界广泛存在，但长期以来一直是微生物学家的一个谜。在三十年的时间里，对一些模式生物的大量研究揭示了它的结构并剖析了其含金属催化剂，但该酶的生理功能仍然难以捉摸。最近对细菌的研究表明，它在硝酸盐和亚硝酸盐还原以及宿主感染期间的抗性中具有一氧化氮还原酶活性。在本研究中，我们从以氨为生长底物的海洋产甲烷古菌中分离并鉴定了一种天然高产的I类HCP。分别以1.45 Å和1.36 Å的分辨率获得的还原态和部分氧化态酶的晶体结构，提供了该古菌酶的精确结构信息。在序列、动力学参数、结构、催化剂构象和内部通道系统方面，与来自其他物种的已充分研究的酶有显著相似性。来自该古菌和许多细菌的酶之间密切的系统发育关系证实了这种相似性。事实上，该古菌的HCP与这些细菌同源物的关系比与任何其他古菌酶的关系更密切。在没有明显一氧化氮来源的情况下，该古菌中HCP的相对高组成型产量对这些古老厌氧菌中该酶的生理功能提出了质疑。
