Similarities in Sulfur Chemistry

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Science  19 Jan 2001:
Vol. 291, Issue 5503, pp. 399
DOI: 10.1126/science.291.5503.399c

Two recent papers provide evidence for an evolutionary relationship between the pathways for molybdenum cofactor biosynthesis, thiamin biosynthesis, and ubiquitin-dependent protein degradation. Rudolph et al. have determined the crystal structure of molybdopterin (MPT) synthase, which comprises a small subunit (MoaD) and a large subunit (MoaE), and is responsible for generating the molybdenum-binding cis-dithiolene group. Wang et al. have determined the solution structure of ThiS, a sulfur carrier protein involved in thiamin biosynthesis.

The structures reveal that ThiS, MoaD, and ubiquitin are similar although the sequence identity between either ThiS or MoaD and ubiquitin is low. The three proteins share unusual sulfur chemistry, too. In ThiS and MoaD, carboxyl-terminal thiocarboxylates act as sulfur carriers, and in ubiquitin a thioester at the carboxyl-terminus is formed by the activating enzyme E1. In all three cases, activation of the terminal carboxylate is ATP-dependent, and the activating enzymes ThiF and MoeB share sequence similarity to each other and to a portion of E1. Finally, in the case of MPT, the formation of an isopeptide bond between the small and large subunits is analogous to the conjugation of ubiquitin to proteins targeted for degradation. — VV

Nature Struct. Biol.8, 42 (2001); Nature Struct. Biol.8, 47 (2001).

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