4ywu | pdb_00004ywu

Structural insight into the substrate inhibition mechanism of NADP+-dependent succinic semialdehyde dehydrogenase from Streptococcus pyogenes

spinqualitylabelsall models 4ywu, resolution 2.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4ywu is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: SO4, SSN Related: 4oht, 4ogd, 4ywv Activity: Succinate-semialdehyde dehydrogenase (NADP(+)), with EC number 1.2.1.79 Resources: FirstGlance, OCA, RCSB, PDBsum Publication Abstract from PubMed Succinic semialdehyde dehydrogenases (SSADHs) are ubiquitous enzymes that catalyze the oxidation of succinic semialdehyde (SSA) to succinic acid in the presence of NAD(P)+, and play an important role in the cellular mechanisms including the detoxification of accumulated SSA or the survival in conditions of limited nutrients. Here, we report the inhibitory properties and two crystal structures of SSADH from Streptococcus pyogenes (SpSSADH) in a binary (ES) complex with SSA as the substrate and a ternary (ESS) complex with the substrate SSA and the inhibitory SSA, at 2.4 A resolution for both structures. Analysis of the kinetic inhibitory parameters revealed significant substrate inhibition in the presence of NADP+ at concentrations of SSA higher than 0.02 mM, which exhibited complete uncompetitive substrate inhibition with the inhibition constant (Ki) value of 0.10 +/- 0.02 mM. In ES-complex of SpSSADH, the SSA showed a tightly bound bent form nearby the catalytic residues, which may be caused by reduction of the cavity volume for substrate binding, compared with other SSADHs. Moreover, structural comparison of ESS-complex with a binary complex with NADP+ of SpSSADH indicated that the substrate inhibition was induced by the binding of inhibitory SSA in the cofactor-binding site, instead of NADP+. Our results provide first structure-based molecular insights into the substrate inhibition mechanism of SpSSADH as the Gram-positive bacterial SSADH. Structural insight into the substrate inhibition mechanism of NADP-dependent succinic semialdehyde dehydrogenase from Streptococcus pyogenes.,Jang EH, Park SA, Chi YM, Lee KS Biochem Biophys Res Commun. 2015 Apr 16. pii: S0006-291X(15)00725-1. doi:, 10.1016/j.bbrc.2015.04.047. PMID:25888791 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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