Crystal structure of molybdopterin synthase and its evolutionary relationship to ubiquitin activation - PubMed (original) (raw)
Crystal structure of molybdopterin synthase and its evolutionary relationship to ubiquitin activation
M J Rudolph et al. Nat Struct Biol. 2001 Jan.
Abstract
Molybdenum cofactor (Moco) biosynthesis is an evolutionarily conserved pathway present in eubacteria, archaea and eukaryotes, including humans. Genetic deficiencies of enzymes involved in Moco biosynthesis in humans lead to a severe and usually fatal disease. Moco contains a tricyclic pyranopterin, termed molybdopterin (MPT), that bears the cis-dithiolene group responsible for molybdenum ligation. The dithiolene group of MPT is generated by MPT synthase, which consists of a large and small subunits. The 1.45 A resolution crystal structure of MPT synthase reveals a heterotetrameric protein in which the C-terminus of each small subunit is inserted into a large subunit to form the active site. In the activated form of the enzyme this C-terminus is present as a thiocarboxylate. In the structure of a covalent complex of MPT synthase, an isopeptide bond is present between the C-terminus of the small subunit and a Lys side chain in the large subunit. The strong structural similarity between the small subunit of MPT synthase and ubiquitin provides evidence for the evolutionary antecedence of the Moco biosynthetic pathway to the ubiquitin dependent protein degradation pathway.
Similar articles
- Structural studies of molybdopterin synthase provide insights into its catalytic mechanism.
Rudolph MJ, Wuebbens MM, Turque O, Rajagopalan KV, Schindelin H. Rudolph MJ, et al. J Biol Chem. 2003 Apr 18;278(16):14514-22. doi: 10.1074/jbc.M300449200. Epub 2003 Feb 5. J Biol Chem. 2003. PMID: 12571227 - Crystal structure of a molybdopterin synthase-precursor Z complex: insight into its sulfur transfer mechanism and its role in molybdenum cofactor deficiency.
Daniels JN, Wuebbens MM, Rajagopalan KV, Schindelin H. Daniels JN, et al. Biochemistry. 2008 Jan 15;47(2):615-26. doi: 10.1021/bi701734g. Epub 2007 Dec 20. Biochemistry. 2008. PMID: 18092812 - Crystal structure of diaminopelargonic acid synthase: evolutionary relationships between pyridoxal-5'-phosphate-dependent enzymes.
Käck H, Sandmark J, Gibson K, Schneider G, Lindqvist Y. Käck H, et al. J Mol Biol. 1999 Aug 27;291(4):857-76. doi: 10.1006/jmbi.1999.2997. J Mol Biol. 1999. PMID: 10452893 - Evolution and function of ubiquitin-like protein-conjugation systems.
Hochstrasser M. Hochstrasser M. Nat Cell Biol. 2000 Aug;2(8):E153-7. doi: 10.1038/35019643. Nat Cell Biol. 2000. PMID: 10934491 Review. - Advancing Our Understanding of Pyranopterin-Dithiolene Contributions to Moco Enzyme Catalysis.
Burgmayer SJN, Kirk ML. Burgmayer SJN, et al. Molecules. 2023 Nov 7;28(22):7456. doi: 10.3390/molecules28227456. Molecules. 2023. PMID: 38005178 Free PMC article. Review.
Cited by
- Binding of IscU and TusA to different but competing sites of IscS influences the activity of IscS and directs sulfur to the respective biomolecular synthesis pathway.
Olivieri P, Klabes M, Crack JC, Lehmann A, Bennett SP, Le Brun NE, Leimkühler S. Olivieri P, et al. Microbiol Spectr. 2024 Jul 9;12(8):e0094924. doi: 10.1128/spectrum.00949-24. Online ahead of print. Microbiol Spectr. 2024. PMID: 38980029 Free PMC article. - Functional redundancy of ubiquitin-like sulfur-carrier proteins facilitates flexible, efficient sulfur utilization in the primordial archaeon Thermococcus kodakarensis.
Hidese R, Ohira T, Sakakibara S, Suzuki T, Shigi N, Fujiwara S. Hidese R, et al. mBio. 2024 Aug 14;15(8):e0053424. doi: 10.1128/mbio.00534-24. Epub 2024 Jul 8. mBio. 2024. PMID: 38975783 Free PMC article. - Beyond Moco Biosynthesis-Moonlighting Roles of MoaE and MOCS2.
Suganuma T. Suganuma T. Molecules. 2022 Jun 10;27(12):3733. doi: 10.3390/molecules27123733. Molecules. 2022. PMID: 35744859 Free PMC article. Review. - Functional elucidation of TfuA in peptide backbone thioamidation.
Liu A, Si Y, Dong SH, Mahanta N, Penkala HN, Nair SK, Mitchell DA. Liu A, et al. Nat Chem Biol. 2021 May;17(5):585-592. doi: 10.1038/s41589-021-00771-0. Epub 2021 Mar 11. Nat Chem Biol. 2021. PMID: 33707784 Free PMC article. - Delineating the phenotypic spectrum of sulfite oxidase and molybdenum cofactor deficiency.
Misko AL, Liang Y, Kohl JB, Eichler F. Misko AL, et al. Neurol Genet. 2020 Jul 14;6(4):e486. doi: 10.1212/NXG.0000000000000486. eCollection 2020 Aug. Neurol Genet. 2020. PMID: 32802950 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Molecular Biology Databases