%0 Journal Article
%T The Biosynthesis of the Molybdenum Cofactor in Escherichia coli and Its Connection to FeS Cluster Assembly and the Thiolation of tRNA
%A Silke Leimk¨¹hler
%J Advances in Biology
%D 2014
%R 10.1155/2014/808569
%X The thiolation of biomolecules is a complex process that involves the activation of sulfur. The L-cysteine desulfurase IscS is the main sulfur mobilizing protein in Escherichia coli that provides the sulfur from L-cysteine to several important biomolecules in the cell such as iron sulfur (FeS) clusters, molybdopterin (MPT), thiamine, and thionucleosides of tRNA. Various proteins mediate the transfer of sulfur from IscS to various biomolecules using different interaction partners. A direct connection between the sulfur-containing molecules FeS clusters, thiolated tRNA, and the molybdenum cofactor (Moco) has been identified. The first step of Moco biosynthesis involves the conversion of 5¡äGTP to cyclic pyranopterin monophosphate (cPMP), a reaction catalyzed by a FeS cluster containing protein. Formed cPMP is further converted to MPT by insertion of two sulfur atoms. The sulfur for this reaction is provided by the L-cysteine desulfurase IscS in addition to the involvement of the TusA protein. TusA is also involved in the sulfur transfer for the thiolation of tRNA. This review will describe the biosynthesis of Moco in E. coli in detail and dissects the sulfur transfer pathways for Moco and tRNA and their connection to FeS cluster biosynthesis. 1. An Introduction to the Importance of Molybdenum and Molybdoenzymes in Bacteria Molybdenum is the only second row transition metal essential for biological systems, which is biologically available as molybdate ion [1]. Molybdenum has a chemical versatility that is useful to biological systems: it is redox-active under physiological conditions (ranging between the oxidation states VI and IV); since the V oxidation state is also accessible, the metal can act as transducer between obligatory two-electron and one-electron oxidation-reduction systems and it can exist over a wide range of redox potentials [2, 3]. The metal forms the active site of molybdoenzymes, which execute key transformations in the metabolism of nitrogen, sulfur, and carbon compounds [3]. The catalyzed reactions are in most cases oxo-transfer reactions; for example, the hydroxylation of carbon centers and the physiological role are fundamental since the reactions include the catalysis of key steps in carbon, nitrogen, and sulfur metabolism. There are two distinct types of molybdoenzymes: molybdenum nitrogenase has a unique molybdenum-iron-sulfur cluster, the [Fe4S3]-(bridging-S)3-[MoFe3S3] center called FeMoco [4]. Nitrogenase catalyzes the reduction of atmospheric dinitrogen to ammonia. All other molybdoenzymes contain the molybdenum cofactor
%U http://www.hindawi.com/journals/ab/2014/808569/