Crystal structure of molybdopterin synthase and its evolutionary relationship to ubiquitin activation.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Rudolph, MJ; Wuebbens, MM; Rajagopalan, KV; Schindelin, H

Published Date

  • January 2001

Published In

Volume / Issue

  • 8 / 1

Start / End Page

  • 42 - 46

PubMed ID

  • 11135669

Pubmed Central ID

  • 11135669

International Standard Serial Number (ISSN)

  • 1072-8368

Digital Object Identifier (DOI)

  • 10.1038/83034

Language

  • eng

Conference Location

  • United States