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1knp
From Proteopedia
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E. coli L-aspartate oxidase: mutant R386L in complex with succinate
Overview
L-Aspartate oxidase (Laspo) catalyzes the conversion of L-Asp to, iminoaspartate, the first step in the de novo biosynthesis of NAD(+). This, bacterial pathway represents a potential drug target since it is absent in, mammals. The Laspo R386L mutant was crystallized in the FAD-bound, catalytically competent form and its three-dimensional structure, determined at 2.5 A resolution in both the native state and in complex, with succinate. Comparison of the R386L holoprotein with the wild-type, apoenzyme [Mattevi, A., Tedeschi, G., Bacchella, L., Coda, A., Negri, A., and Ronchi, S. (1999) Structure 7, 745-756] reveals that cofactor, incorporation leads to the ordering of two polypeptide segments (residues, 44-53 and 104-141) and to a 27 degree rotation of the capping domain. This, motion results in the formation of the active site cavity, located at the, interface between the capping domain and the FAD-binding domain. The, structure of the succinate complex indicates that the cavity surface is, decorated by two clusters of H-bond donors that anchor the ligand, carboxylates. Moreover, Glu121, which is strictly conserved among Laspo, sequences, is positioned to interact with the L-Asp alpha-amino group. The, architecture of the active site of the Laspo holoenzyme is remarkably, similar to that of respiratory fumarate reductases, providing strong, evidence for a common mechanism of catalysis in Laspo and flavoproteins of, the succinate dehydrogenase/fumarate reductase family. This implies that, Laspo is mechanistically distinct from other flavin-dependent amino acid, oxidases, such as the prototypical D-amino acid oxidase.
About this Structure
1KNP is a Single protein structure of sequence from Escherichia coli with NA, FAD and SIN as ligands. Active as L-aspartate oxidase, with EC number 1.4.3.16 Full crystallographic information is available from OCA.
Reference
Structure of FAD-bound L-aspartate oxidase: insight into substrate specificity and catalysis., Bossi RT, Negri A, Tedeschi G, Mattevi A, Biochemistry. 2002 Mar 5;41(9):3018-24. PMID:11863440
Page seeded by OCA on Tue Nov 20 19:26:09 2007
