Structure of the molybdenum-cofactor biosynthesis protein MoaB ofEscherichia coli

Abstract

The moaABC operon of Escherichia coli is involved in early steps of the biosynthesis of the molybdenum-binding cofactor molybdopterin, but the precise functions of the cognate proteins are not known. The crystal structure of the MoaB protein from E. coli was determined by multiple anomalous dispersion at 2.1 angstroms A resolution and refined to an R factor of 20.4% (Rfree = 25.0%). The protein is a 32-symmetric hexamer, with the monomers consisting of a central beta-sheet flanked by helices on both sides. The overall fold of the monomer is similar to those of the MogA protein of E. coli, the G-domains of rat and human gephyrin and the G-domains of Cnx1 protein from A. thaliana, all of which are involved in the insertion of an unknown molybdenum species into molybdopterin to form the molybdenum cofactor. Furthermore, the MoaB protein shows significant sequence similarity to the cinnamon protein from Drosophila melanogaster. In addition to other functions, all these proteins are involved in the biosynthesis of the molybdenum cofactor and have been shown to bind molybdopterin. The close structural homology to MogA and the gephyrin and Cnx1 domains suggests that MoaB may bind a hitherto unidentified pterin compound, possibly an intermediate in molybdopterin biosynthesis.

Structural Basis of Thermal Stability of the Tungsten Cofactor Synthesis Protein MoaB from Pyrococcus furiosus

“…As no co-purified MPT or MPT-AMP was detected in PfuMoaB, the observed electron density was attributed to components of the crystallization solution. In crystal structures of PfuMoaB homologues, E. coli MogA and E. coli MoaB, a sulfate anion was detected in the same position close to the Gly-Gly-Thr-Gly motif, most probably mimicking the phosphate of MPT [26], [27]. PfuMoaB crystals were grown in a solution containing 2-(N-morpholino)ethanesulfonic acid (MES), which with its negatively charged sulfonate part resembles sulfate or phosphate.…”

Molybdenum cofactor biosynthesis and deficiency

“…[156] Cnx6 [157] Cnx5 [94] MOCS2A [42] MOCS2B [42] MOCS3 [158] 3 a MogA [61,103] MoaB [70,159] CnxE (N) [40] Cnx1 (C) [106,160] Geph. (N) [43,106] 4 a MoeA [64,109] CnxE (C) [40] Cnx1 (N) [160] Geph.…”

Genetic characterization of moaB mutants of Escherichia coli

“…Both the primary sequence and crystal structure of MoaB show strong similarities with the MogA protein (Bader et al, 2004; Bevers et al, 2008; Sanishvili et al, 2004), which catalyzes formation of the MPT-AMP intermediate during the Mo-insertion step into Moco. Indeed, in the archaeon Pyrococcus furiosus , which lacks a MogA protein, its MoaB enzyme is responsible for the MPT adenylylation (Bevers et al, 2008).…”