9yq9

Clostridium leptum Carboxyaminopropylagmatine Dehydrogenase Apo

spinqualitylabelsall models 9yq9, resolution 2.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9yq9 is a 4 chain structure with sequence from Clostridium leptum. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.5Å Ligands: GOL Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A7VSG1_9FIRM Publication Abstract from PubMed Putrescine has long been considered the initiating substrate for aspartate semialdehyde-dependent bacterial spermidine biosynthesis. However, two recent studies identified a variant pathway in which agmatine serves as the preferred substrate. This variation appears to be common, but the mechanistic basis for substrate preference was unknown. Here, we investigate the aspartate semialdehyde-dependent dehydrogenases from Bacteroides fragilis and Clostridium leptum using steady-state and transient-state kinetic assays, mass spectrometry, thermal shift protein stability assays, X-ray crystallography, small-angle X-ray scattering, and computational modeling. Both enzymes exhibit dramatically enhanced catalytic efficiency with agmatine, demonstrating that these homologs function as carboxyaminopropylagmatine dehydrogenases rather than carboxyspermidine dehydrogenases. Agmatine enhances NADPH binding affinity by 34-fold, whereas putrescine has a modest effect and at concentrations less likely to be physiologically relevant. Apo crystal structures and small angle X-ray scattering analysis reveal substantial ligand-dependent conformational rearrangements involving both global domain and active-site loop motions. These structural transitions, together with thermal stability measurements and transient-state binding assays, support an induced-fit mechanism in which agmatine promotes conformational rearrangements that enhance NADPH-binding. Comparative sequence analysis of homologs and ligand docking lead us to propose an active-site recognition loop governing discrimination between agmatine, putrescine, and diaminopropane substrates. Together, these findings redefine the substrate specificity of the B. fragilis and C. leptum enzymes, establish a mechanistic model for agmatine-dependent catalysis in alternative spermidine biosynthesis, and provide a testable framework for predicting substrate specificity across this family of bacterial polyamine biosynthetic enzymes. Agmatine as the initiating substrate for aspartate semialdehyde-dependent bacterial spermidine biosynthesis.,Ostlund JC, Johnston LA, Pardoe MA, Bustillos IM, Bizzell ML, Jones SJ, Lee DF, McFarlane JS J Biol Chem. 2026 Sep 17:113570. doi: 10.1016/j.jbc.2026.113570. PMID:42754158 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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