Shared function and moonlighting proteins in molybdenum cofactor biosynthesis

Abstract

Abstract:The biosynthesis of the molybdenum cofactor (Moco) is a highly conserved pathway in bacteria, archaea and eukaryotes. The molybdenum atom in Mococontaining enzymes is coordinated to the dithiolene group of a tricyclic pyranopterin monophosphate cofactor. The biosynthesis of Moco can be divided into three conserved steps, with a fourth present only in bacteria and archaea:(1) formation of cyclic pyranopterin monophosphate, (2) formation of molybdopterin (MPT), (3) insertion of molybdenum into MPT to form Mo-MPT, and (4) additional modification of Mo-MPT in bacteria with the attachment of a GMP or CMP nucleotide, forming the dinucleotide variants of Moco. While the proteins involved in the catalytic reaction of each step of Moco biosynthesis are highly conserved among the Phyla, a surprising link to other cellular pathways has been identified by recent discoveries. In particular, the pathways for FeS cluster assembly and thio-modifications of tRNA are connected to Moco biosynthesis by sharing the same protein components. Further, proteins involved in Moco biosynthesis are not only shared with other pathways, but additionally have moonlighting roles. This review gives an overview of Moco biosynthesis in bacteria and humans and highlights the shared function and moonlighting roles of the participating proteins.

Iron Sulfur and Molybdenum Cofactor Enzymes Regulate the Drosophila Life Cycle by Controlling Cell Metabolism

“…Turning to Moco biosynthesis, an ancient, ubiquitous and highly conserved pathway underpinning molybdenum biochemistry (Rajagopalan, 1997 ; Mendel and Leimkühler, 2015 ; Leimkühler, 2017 ), it can be divided into three major steps: (i) GTP is converted to cPMP, (ii) cPMP is converted to MPT by generation of the dithiolene group, and (iii) molybdate is then ligated to MPT forming Moco (Figure 1 ). Three fly genes involved in Moco biosynthesis have attracted individual attention: (i) Mocs1 (formerly known as low xanthine dehydrogenase, lxd ) encoding a mitochondrial Fe-S enzyme that converts 5′-guanosine triphosphate (GTP) to cyclic pyranopterin monophosphate (cPMP) (Keller and Glassman, 1964 ; Courtright, 1975 ; Duke et al, 1975 ; Bogaart and Bernini, 1981 ; Schott et al, 1986 ; Ho et al, 1992 ; Tahoe et al, 2002 ), (ii) cinnamon ( cin ) encoding a gephyrin homolog that inserts molybdate into MPT (Baker, 1973 ; Browder and Williamson, 1976 ; Kamdar et al, 1994 ; Wittle et al, 1999 ), and (iii) maroon-like (mal) that encodes a Moco sulfurase (Mitchell and Glassman, 1959 ; Hubby and Forrest, 1960 ; Finnerty et al, 1970 ; Marsh and Wieschaus, 1977 ; Kamleh et al, 2009 ).…”

“…In D. melanogaster , the pioneering work of Maria Moltó and co-workers has almost exclusively focused on the Drosophila frataxin homolog describing what goes wrong when Fe-S biosynthesis is disrupted in flies (reviewed in Mandilaras et al, 2013 ; Tang and Zhou, 2013b ; Zhu et al, 2014 ; Calap-Quintana et al, 2017 ). Furthermore, we describe the biosynthesis of Moco (Rajagopalan, 1997 ; Mendel and Leimkühler, 2015 ; Leimkühler, 2017 ), whose basic structure has two sulfur atoms of the tricyclic pyranopterin molecule molybdopterin (MPT) coordinating the Mo atom (Rajagopalan et al, 1982 ). Work on Moco enzymes in Drosophila started in the fifties and Victoria Finnerty studied the Moco biosynthetic pathway during the last quarter of the twentieth century (Kamdar et al, 1997 ).…”

Coordinated regulation of nitrogen fixation and molybdate transport by molybdenum

“…Mo mobilization for FeMoco assembly is mediated by NifQ. For details on Moco and FeMoco biosynthesis, see recent reviews (Hu and Ribbe, ; Curatti and Rubio, ; Yang et al , ; Mendel and Leimkühler, ; Hu and Ribbe, ; Leimkühler, ). VFeco and FeFeco are structurally similar to FeMoco but differ in several aspects.…”

“…With the exception of Mo-nitrogenase, all other molybdoenzymes contain the molybdenum cofactor Moco or a Moco derivative (Mendel and Leimkühler, 2015;Leimkühler, 2017). Moco biosynthesis proceeds in three steps (Fig.…”

“…To cope with Mo limitation, 89% of Mo-utilizing bacteria, regardless of whether diazotrophic or not, are predicted to synthesize highly efficient ModABC transporters (Peng et al, 2018). They import molybdate (MoO 4 2-), the only (Hu and Ribbe, 2011;Curatti and Rubio, 2014;Yang et al, 2014;Mendel and Leimkühler, 2015;Hu and Ribbe, 2016;Leimkühler, 2017). VFeco and FeFeco are structurally similar to FeMoco but differ in several aspects.…”