1tv7
From Proteopedia
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Structure of the S-adenosylmethionine dependent Enzyme MoaA
Overview
The MoaA and MoaC proteins catalyze the first step during molybdenum, cofactor biosynthesis, the conversion of a guanosine derivative to, precursor Z. MoaA belongs to the S-adenosylmethionine (SAM)-dependent, radical enzyme superfamily, members of which catalyze the formation of, protein and/or substrate radicals by reductive cleavage of SAM by a, [4Fe-4S] cluster. A defined in vitro system is described, which generates, precursor Z and led to the identification of 5'-GTP as the substrate. The, structures of MoaA in the apo-state (2.8 angstroms) and in complex with, SAM (2.2 angstroms) provide valuable insights into its mechanism and help, to define the defects caused by mutations in the human ortholog of MoaA, that lead to molybdenum cofactor deficiency, a usually fatal disease, accompanied by severe neurological symptoms. The central core of each, subunit of the MoaA dimer is an incomplete triosephosphate isomerase, barrel formed by the N-terminal part of the protein, which contains the, [4Fe-4S] cluster typical for SAM-dependent radical enzymes. SAM is the, fourth ligand to the cluster and binds to its unique Fe as an N/O chelate., The lateral opening of the incomplete triosephosphate isomerase barrel is, covered by the C-terminal part of the protein containing an additional, [4Fe-4S] cluster, which is unique to MoaA proteins. Both FeS clusters are, separated by approximately 17 angstroms, with a large active site pocket, between. The noncysteinyl-ligated unique Fe site of the C-terminal, [4Fe-4S] cluster is proposed to be involved in the binding and activation, of 5'-GTP.
About this Structure
1TV7 is a Single protein structure of sequence from Staphylococcus aureus with SO4 and SF4 as ligands. Full crystallographic information is available from OCA.
Reference
Crystal structure of the S-adenosylmethionine-dependent enzyme MoaA and its implications for molybdenum cofactor deficiency in humans., Hanzelmann P, Schindelin H, Proc Natl Acad Sci U S A. 2004 Aug 31;101(35):12870-5. Epub 2004 Aug 18. PMID:15317939
Page seeded by OCA on Wed Nov 21 03:37:17 2007
