Funck D, Sinn M, Fleming J R, Stanoppi M, Dietrich J, López-Igual R, Mayans O, Hartig J S
Department of Chemistry, University of Konstanz, Konstanz, Germany.
Department of Biology, University of Konstanz, Konstanz, Germany.
Nature. 2022 Mar;603(7901):515-521. doi: 10.1038/s41586-022-04490-x. Epub 2022 Mar 9.
Nitrogen availability is a growth-limiting factor in many habitats, and the global nitrogen cycle involves prokaryotes and eukaryotes competing for this precious resource. Only some bacteria and archaea can fix elementary nitrogen; all other organisms depend on the assimilation of mineral or organic nitrogen. The nitrogen-rich compound guanidine occurs widely in nature, but its utilization is impeded by pronounced resonance stabilization, and enzymes catalysing hydrolysis of free guanidine have not been identified. Here we describe the arginase family protein GdmH (Sll1077) from Synechocystis sp. PCC 6803 as a Ni-dependent guanidine hydrolase. GdmH is highly specific for free guanidine. Its activity depends on two accessory proteins that load Ni instead of the typical Mn ions into the active site. Crystal structures of GdmH show coordination of the dinuclear metal cluster in a geometry typical for arginase family enzymes and allow modelling of the bound substrate. A unique amino-terminal extension and a tryptophan residue narrow the substrate-binding pocket and identify homologous proteins in further cyanobacteria, several other bacterial taxa and heterokont algae as probable guanidine hydrolases. This broad distribution suggests notable ecological relevance of guanidine hydrolysis in aquatic habitats.
氮的可利用性是许多生境中的一个生长限制因素，全球氮循环涉及原核生物和真核生物对这一珍贵资源的竞争。只有一些细菌和古菌能够固定单质氮；所有其他生物都依赖于对矿物氮或有机氮的同化作用。富含氮的化合物胍在自然界中广泛存在，但其利用受到显著共振稳定作用的阻碍，且尚未发现催化游离胍水解的酶。在此，我们将来自集胞藻属PCC 6803的精氨酸酶家族蛋白GdmH（Sll1077）描述为一种依赖镍的胍水解酶。GdmH对游离胍具有高度特异性。其活性依赖于两种辅助蛋白，这两种蛋白将镍而非典型的锰离子加载到活性位点中。GdmH的晶体结构显示双核金属簇以精氨酸酶家族酶典型的几何构型配位，并允许对结合的底物进行建模。一个独特的氨基末端延伸和一个色氨酸残基使底物结合口袋变窄，并在其他蓝细菌、其他几个细菌类群和不等鞭毛藻中鉴定出同源蛋白可能是胍水解酶。这种广泛分布表明胍水解在水生生境中具有显著的生态相关性。
